This article was downloaded by you on: Apr 03, 2016 Bangladesh J Pharmacol 2016; 11: 433-452 A Journal of the Bangladesh Pharmacological Society (BDPS) Journal homepage: www.banglajol.info Abstracted/indexed in Academic Search Complete, Asia Journals Online, Bangladesh Journals Online, Biological Abstracts, BIOSIS Previews, CAB Abstracts, Current Abstracts, Directory of Open Access Journals, EMBASE/Excerpta Medica, Google Scholar, HINARI (WHO), International Pharmaceutical Abstracts, Open J-gate, Science Citation Index Expanded, SCOPUS and Social Sciences Citation Index; ISSN: 1991-0088 Chemical and bioactive diversities of marine sponge Neopetrosia Haitham Qaralleh Department of Medical Support, Al-Balqa Applied University, Al-Karak University College, Al-Karak, Jordan. Article Info Received: Accepted: Available Online: Abstract 26 January 2016 21 March 2016 3 April 2016 DOI: 10.3329/bjp.v11i2.26611 Cite this article: Qaralleh H. Chemical and bioactive diversities of the marine sponge Neopetrosia. Bangladesh J Pharmacol. 2016; 11: 433-52. The marine sponge Neopetrosia contains about 27 species that is highly distributed in Indian Ocean, Atlantic Ocean (Caribbean Sea) and Pacific Ocean. It has proven to be valuable to the discovery of medicinal products due to the presence of various types of compounds with variable bioactivities. More than 85 compounds including alkaloids, quinones, sterols and terpenoids were isolated from this genus. Moreover, the crude extracts and the isolated compounds revealed activities such as antimicrobial, anti-fouling, anti-HIV, cytotoxic, anti-tumor, anti-oxidant, anti-protozoal, anti-inflammatory. Because only 9 out of 27 species of the genus Neopetrosia have been chemically studied thus far, there are significant opportunities to find out new chemical constituents from this genus. Introduction Marine sponges represent the major rich organisms with promising active pharmaceutical metabolites. The interest for drugs discovery in sponges has started since 1950s due to the discovery of the nucleosides spongothymidine and spongouridine from the marine sponge Cryptotethya crypta (Laport et al., 2009). Both metabolites were later developed to ara-C, the first marine-derived anti-cancer agent and the antiviral drug ara-A (Proksch et al., 2002). Later, several promising metabolites were discovered from marine sponges with different biological activities including antimicrobial and anti-cancer (Mayer et al., 2013). So far, more than 36% of the metabolites discovered from marine organisms were isolated from the sponges. Neopetrosia is a genus of marine sponge that belongs to the phylum Porifera, the class Demospongia, of the order Haploscleridae, and family Petrosiidae. The genus was established by the Max Walker de Laubenfels in 1932. It contains about 27 species that is highly distributed in Indian Ocean, Atlantic Ocean (Caribbean Sea) and Pacific Ocean. Neopetrosia has received great attention in natural product chemistry. Several studies have been conducted lead to report the isolation of more than 85 metabolites. Therefore, the aim of this paper is to review the Neopetrosia genus, primarily focusing on their phytochemical characteristics and their biological activities. Sponge species is identified based on the external morphological characteristics and spicules and skeleton characteristics. However, sponges are among the most difficult organisms to identify. Misidentification of this organism is common (Hooper et al., 2000; Qaralleh et al., 2011). Misidentification of sponges may lead to failure in the prediction of the chemical compo-sitions. Recently, many species belong to the Xestospongia or Petrosia genera were transferred to Neopetrosia genus. In this study, World Register of Marine Species (www.marinespecies.org) was used to get the species scientific and synonymised names (Table I). Both names were used as a search keys in order to find the relevant literature about each species. The literature was collected by searching the major scientific databases including Marinlit, PubMed, SciFinder, Science direct, Scopus, Medline and Google Scholar. The data were then organised in Table which represented the species name, isolated compounds, place of collection and the bioactivities. 434 Bangladesh J Pharmacol 2016; 11: 433-452 Table I Scientific names and synonym (s) for neopetrosia species Species Synonym (s) Distribution 1 Neopetrosia carbonaria (Lamarck, 1814) Adocia carbonaria (Lamarck, 1814) Oceanapia carbonaria (Lamarck, 1814) Pachychalina carbonaria (Lamarck, 1814) Pellina carbonaria (Lamarck, 1814) Spongia carbonaria Lamarck, 1814 Thalysias carbonaria (Lamarck, 1814) Xestospongia carbonaria (Lamarck, 1814) Caribbean Sea 2 Neopetrosia chaliniformis (Thiele, 1899) Petrosia (Petrosia) chaliniformis (Thiele, 1899) Petrosia chaliniformis (Thiele, 1899) Indonesia 3 Neopetrosia compacta (Ridley and Dendy, 1886) Petrosia similis var. compacta (Ridley and Dendy, 1886) Philippines 4 Neopetrosia contignata (Thiele, 1899) Haliclona contignata (Thiele, 1899) Petrosia contignata (Thiele, 1899) Indonesia East African Coral Coast Gulf of Aden Southern Red Sea 5 Neopetrosia cylindrica (Lamarck, 1815) Caribbean Sea 6 Neopetrosia delicatula (Dendy, 1905) Alcyonium cylindricum (Lamarck, 1815) Xestospongia cylindrica (Lamarck, 1815) Petrosia similis var. delicatula (Dendy, 1905) 7 Neopetrosia densissima (Wilson, 1904) Petrosia similis var. densissima (Wilson, 1904) 8 Neopetrosia dominicana (Pulitzer-Finali, 1986) Xestospongia dominicana (Pulitzer-Finali, 1986) 9 Neopetrosia exigua (Kirkpatrick, 1900) 10 Neopetrosia granulosa (Wilson, 1925) Haliclona exigua (Kirkpatrick, 1900) Neopetrosia pandora (de Laubenfels, 1954) Petrosia exigua (Kirkpatrick, 1900) Xestospongia exigua (Kirkpatrick, 1900) Xestospongia pacifica (Kelly Borges and Bergquist, 1988) Petrosia similis var. granulosa (Wilson, 1925) 11 Neopetrosia halichondrioides Dendy, 1905 Petrosia similis var.halichondrioides (Dendy, 1905) 12 Neopetrosia massa (Ridley & Dendy, 1886) Petrosia similis var. massa (Ridley and Dendy, 1886) 13 Neopetrosia perforata (Lévi, 1959) Haliclona perforata (Lévi, 1959) 14 Neopetrosia problematica (de Laubenfels, 1930) Dictyonella problematica (de Laubenfels, 1930) Haliclona problematica (de Laubenfels, 1930) Prianos problematicus (de Laubenfels, 1930) Northern California 15 Neopetrosia proxima (Duchassaing and Michelotti, 1864) Densa araminta (de Laubenfels, 1934) Thalysias proxima (Duchassaing and Michelotti, 1864) Xestospongia proxima (Duchassaing and Michelotti, 1864) Caribbean Sea North Atlantic Ocean 16 Neopetrosia rava (Thiele, 1899) Petrosia rava (Thiele, 1899) Indonesia 17 Neopetrosia retiderma (Dendy, 1922) 18 Neopetrosia rosariensis (Zea and Rützler, 1983) Halichondria retiderma (Dendy, 1922) Haliclona retiderma (Dendy, 1922) Xestospongia rosariensis (Zea and Rützler, 1983) Seychelles Indian Ocean Caribbean Sea North Atlantic Ocean According to World Register of Marine Species Sri Lanka South India Galapagos Dominican Republic Greater Antilles Indian Ocean Papua New Guinea Singapore Strait East African Coral Coast Philippines Sri Lanka South India Falkland Islands Malvinas/Falklands Gulf of Guinea Islands Sao Tome and Principe exclusive economic zone 435 Bangladesh J Pharmacol 2016; 11: 433-452 Table I Scientific names and synonym (s) for neopetrosia species (Cont.) Species Synonym (s) Distribution 19 Neopetrosia sapra (de Laubenfels, 1954) Xestospongia sapra (de Laubenfels, 1954) East Caroline Islands Micronesia 20 Neopetrosia seriata (Hentschel, 1912) Petrosia seriata (Hentschel, 1912) Petrosia similis var. seriata (Hentschel, 1912) Arafura Sea Indonesian exclusive Economic Zone Southern Vietnam Vietnamese exclusive Economic Zone 21 Neopetrosia similis (Ridley and Dendy, 1886) Chalina similis (Ridley and Dendy, 1886) Petrosia similis (Ridley and Dendy, 1886) Agulhas Bank Eastern Philippines Philippines exclusive economic zone South African exclusive economic zone South India, Sri Lanka 22 Neopetrosia subtriangularis (Duchassaing, 1850) Haliclona doria (de Laubenfels, 1936) Haliclona longleyi (de Laubenfels, 1932) Haliclona subtriangularis (Duchassaing and Michelotti, 1864) Neopetrosia longleyi (De Laubenfels, 1932) Pachychalina rugosa (Duchassaing and Michelotti, 1864) Pachychalina rugosa var. rubens (Arndt, 1927) Schmidtia aulopora (Schmidt, 1870) Spongia subtriangularis (Duchassaing, 1850) Thalysias rugosa (Duchassaing and Michelotti, 1864) Thalysias subtriangularis (Duchassaing, 1850) Thalysias subtriangularis var. cylindrica (Duchassaing and Michelotti, 1864) Thalysias subtriangularis var. lyriformis (Duchassaing and Michelotti, 1864) Xestospongia subtriangularis (Duchassaing, 1850) Bahamas Caribbean Sea Caribbean Sea Netherlands Netherlands Antilles United States 23 Neopetrosia tenera (Carter, 1887) Thalysias tenera (Carter, 1887) Andaman and Nicobar Islands Myanmar 24 Neopetrosia truncata (Ridley and Dendy, 1886) Petrosia truncata (Ridley and Dendy, 1886) Philippines 25 Neopetrosia tuberosa (Dendy, 1922) Haliclona tuberosa (Dendy, 1922) Oceanapia tuberosa (Dendy, 1922) Reniera tuberosa (Dendy, 1922) Indian Ocean Saya de Malha Seychelles Cargados Carajos/Tromelin Island Western Arabian Sea 26 Neopetrosia vanilla (de Laubenfels, 1930) Haliclona vanilla (de Laubenfels, 1930) Xestospongia vanilla (de Laubenfels, 1930) California North Pacific Ocean 27 Neopetrosia zumi (Ristau, 1978) Haliclona (Reniera) zumi (Ristau, 1978) Toxadocia zumi (Ristau, 1978) California North Pacific Ocean 436 Bangladesh J Pharmacol 2016; 11: 433-452 isolated from N. exigua and only two have been isolated from N. similes (14 and 15). Chemical Composition More than 85 compounds have been isolated from Neopetrosia species. These compounds were classified into alkaloids, quinones, sterols and terpenoids (Table II). Four macrocyclic quinolizidines were isolated from Australian sponge N. exigua (Xestospongia exigua) namely xestospongin A (1), B (2), C (3) and D (4) (Nakagawa et al., 1984). Several araguspongines alkaloids were obtained from a red sea sponge N. exigua (Haliclona exigua) including (+)-araguspongine A (5), (+) -araguspongine B (6), (+)-araguspongine C (7), (+)araguspongine D (1), (-)-araguspongine E (8), and (+)xestospongin B (9) (Venkateswarlu et al., 1994; Venkateswara et al., 1998). (+)-araguspongine K (10) and (+)-araguspongine L (11) were isolated from a red sea sponge N. exigua (Xestospongia exigua) (Orabi et al., 2002). Araguspongin C (12) was found from n-butanol Alkaloids More than 44 alkaloids have been isolated. These alkaloids were macrocyclic quinolizidines, 3-alkylpyridine alkaloids, pyridoacridine alkaloids and others. Macrocyclic quinolizidines Nineteen macrocyclic quinolizidines alkaloids have been reported from this genus. Several macrocyclic quinolizidines alkaloids (1-13 and 16-19) have been N H N H H H O H O HO H O N N O H H H O O HO H N (+)-Araguaspongin D N HO N Xestospongin B (2) N N H O H O O H O H Xestospongin D (4) N N H O H O O N N N H3C Xestospongin C (3) HO H O H H Xestospongin A (1)= H O H OH O N H N (+)-Araguspongine A (5) (+)-Araguspongine B (6) (+)-Araguspongine C (7) (-)-Araguspongine E (8) OH + N N H O O H N (+)-Xestospongin B (9) HO H O O N N H N HO H O O HO H + N OH OH H O O H OH N (+)-Araguspongine K (10) (+)-Araguspongine L (11) Araguspongine C (12) Bangladesh J Pharmacol 2016; 11: 433-452 Table II Chemical constituent of the Neopetrosia genus No. Compound class and name Source Reference Alkaloids Macrocyclic quinolizidines 1 Xestospongin A ((+)-araguspongine D) N. exigua (Xestospongia exigua) Nakagawa et al., 1984; Venkateswarlu et al., 1994, Venkateswara et al., 1998; Liu et al., 2004; Li et al., 2011 2 Xestospongin B N. exigua (Xestospongia exigua) Nakagawa et al., 1984 3 Xestospongin C N. exigua (Xestospongia exigua) Nakagawa et al., 1984 4 Xestospongin D N. exigua (Xestospongia exigua) Nakagawa et al., 1984 5 (+)-Araguspongine A N. exigua (Haliclona exigua) Venkateswarlu et al., 1994; Venkateswara et al., 1998 6 (+)-Araguspongine B N. exigua (Haliclona exigua) N. exigua (Xestospongia exigua) Venkateswarlu et al., 1994; Venkateswara et al., 1998, Liu et al., 2004 7 (+)-Araguspongine C N. exigua (Haliclona exigua) Venkateswarlu et al., 1994; Venkateswara et al., 1998 8 (-)-Araguspongine E N. exigua (Haliclona exigua) Venkateswarlu et al., 1994; Venkateswara et al., 1998 9 (+)-Xestospongin B N. exigua (Haliclona exigua) Venkateswarlu et al., 1994; Venkateswara et al., 1998 10 (+)-Araguspongine K N. exigua (Xestospongia exigua) Orabi et al., 2002 11 (+)-Araguspongine L N. exigua (Xestospongia exigua) Orabi et al., 2002 . Dube et al., 2007 12 Araguspongin C N. exigua (Haliclona exigua) 13 Xestosin A N. exigua (Xestospongia exigua) Iwagawa et al., 2000 14 Petrosin N. similis Venkateshwar Goud et al., 2003 15 Petrosin-A N. similis Venkateshwar Goud et al., 2003 16 Araguspongine M N. exigua (Xestospongia exigua) Liu et al., 2004 17 9'-Epi-3ß,3'ß– dimethylxestospongin C N. exigua Li et al., 2011 18 3ß,3'ß– Dimethylxestospongin C N. exigua Li et al., 2011 19 Demethylxestopongin B N. exigua Li et al., 2011 3-Alkylpyridine alkaloids 20 Renieramycin J Neopetrosia sp. Oku et al., 2003 21 Renieramycin A Neopetrosia sp. Nakao et al., 2004 22 Exiguamine A Neopetrosia exigua Brastianos et al., 2006 23 Njaoamines G Neopetrosia sp. Sorek et al., 2007 24 Njaoamines H Neopetrosia sp. Sorek et al., 2007 25 1,2,3,4-tetrahydroquinolin4-one Neopetrosia sp. Sorek et al., 2007 26 Neopetrosiamine A Neopetrosia proxima Wei et al., 2010 27 Xestoproxamine A N. proxima Morinaka and Molinski, 2011 28 Xestoproxamine B N. proxima Morinaka and Molinski, 2011 29 Xestoproxamine C N. proxima Morinaka and Molinski, 2011 Pyridoacridine alkaloids 30 1-Hydroxydeoxyamphimedine N. carbonaria Wei et al., 2010 31 3-Hydroxydeoxyamphimedine N. carbonaria Wei et al., 2010 32 Debromopetrosamine N. carbonaria Wei et al., 2010 437 438 Bangladesh J Pharmacol 2016; 11: 433-452 Table II Chemical constituent of the Neopetrosia genus (Cont.) No. Compound class and name Source Reference 33 Amphimedine N. carbonaria Wei et al., 2010 34 Neoamphimedine N. carbonaria Wei et al., 2010 35 Deoxyamphimedine N. carbonaria Wei et al., 2010 Others alkaloids 36 Motuporamines A N. exigua (Xestospongia exigua) Williams et al., 1998; Williams et al., 2002 37 Motuporamines B N. exigua (Xestospongia exigua) Williams et al., 1998; Williams et al., 2002 38 Motuporamines C N. exigua (Xestospongia exigua) Williams et al., 1998; Williams et al., 2002 39 Motuporamines D N. exigua (Xestospongia exigua) Williams et al., 1998; Williams et al., 2002 40 Motuporamines E N. exigua (Xestospongia exigua) Williams et al., 1998; Williams et al., 2002 41 Motuporamines F N. exigua (Xestospongia exigua) Williams et al., 1998; Williams et al., 2002 42 Motuporamines - a mixture of G, H, and I N. exigua (Xestospongia exigua) Williams et al., 1998; Williams et al., 2002 43 7,8-Dihydrotubastrine N. contignata (Petrosia cf. contignata) Sperry and Crews, 1998 44 4-Deoxy-7,8-dihydrotubastrine N. contignata (Petrosia cf. contignata) Sperry and Crews, 1998 Quinones 45 Tetrahydrohalenaquinone A N. carbonaria Alviet al., 1993 46 Tetrahydrohalenaquinone B N. carbonaria Alvi et al., 1993 47 14-Methoxyhalenaquinone N. carbonaria Alvi et al., 1993 48 Halenquinone N. carbonaria N. exigua (Xestospongia exigua) Alvi et al., 1993 49 Halenquinol N. carbonaria N. sapra N. seriata (Petrosia seriata) Alvi et al., 1993 50 Halenquinol sulfate Xestoquinol sulfate N. carbonaria N. sapra Alvi et al., 1993; Kobayashi et al., 1985; Kobayashi et al., 1992 51 Xestoquinone N. carbonaria Alvi et al., 1993 52 Xestoquinolide A N. carbonaria Alvi et al., 1993 53 Xestoquinolide B N. carbonaria Alvi et al., 1993 54 Xestosaprol A N. sapra Kobayashi et al., 1992 55 Xestosaprol B N. sapra Kobayashi et al., 1992 56 Xestosaprol C N. sapra Kubota et al., 2008 57 Neopetrosiquinone A N. proxima Winder et al., 2011 58 Neopetrosiquinone B N. proxima Winder et al., 2011 59 1,2-Dihydroisoquinoline N. similis (Petrosia similis) Ramesh et al., 1999 60 Isoquinolinequinone N. similis (Petrosia similis) Ramesh et al., 1999 61 Galactosyl diacylglycerols N. exigua (Xestospongia exigua) Liu et al., 2004 62 Galactosyl diacylglycerols N. exigua (Xestospongia exigua) Liu et al., 2004 63 Galactosyl diacylglycerols N. exigua (Xestospongia exigua) Liu et al., 2004 Sterols Bangladesh J Pharmacol 2016; 11: 433-452 439 Table II Chemical constituent of the Neopetrosia genus (Cont.) No. Compound class and name Source Reference 64 24-Methyl cholesterol N. exigua (Xestospongia exigua) Liu et al., 2004 65 5, 6-Dihydrocholesterol N. exigua (Xestospongia exigua) Liu et al., 2004 N. exigua (Xestospongia exigua) Liu et al., 2004; Cerqueira et al., 2003 67 5 , 8 -Epidioxy sterols N. exigua (Xestospongia exigua) Liu et al., 2004 68 5 , 8 -Epidioxy sterols N. exigua (Xestospongia exigua) Liu et al., 2004 69 5 , 8 -Epidioxy sterols N. exigua (Xestospongia exigua) Liu et al., 2004 70 5 , 8 -Epidioxy-24 ethylcholest-6-en-3-ol N. exigua (Xestospongia exigua) Cerqueira et al., 2003 71 Clionasterol N. exigua (Xestospongia exigua) Cerqueira et al., 2003 72 Clionasterol monoacetate N. exigua (Xestospongia exigua) Cerqueira et al., 2003 73 Xestobergsterol A N. contignata (Petrosia cf. contignata) Sperry and Crews, 1998 66 -Sitosterol Terpenoids 74 Xestovanin A N. vanilla (X. vanilla) Northcote and Andersen, 1989 75 Secoxestovanin A N. vanilla (X. vanilla) Northcote and Andersen, 1989 76 Isoxestovanin A N. vanilla (Xestospongia vanilla) Morris et al., 1991 77 Xestovanins B N. vanilla (Xestospongia vanilla) Morris et al., 1991 78 Xestovanins C N. vanilla (Xestospongia vanilla) Morris et al., 1991 79 Dehydroxestovanin C N. vanilla (Xestospongia vanilla) Morris et al., 1991 80 81 82 Xestodiol Xestenone Xestolide N. vanilla N. vanilla N. vanilla Northcote and Andersen, 1989; Morris et al., 1991 Northcote and Andersen, 1989 Morris et al., 1991 83 Secoxestenone N. vanilla Northcote and Andersen, 1989 84 Secodehydroxestovanine A N. vanilla Morris et al., 1991 Neopetrosia sp. Williams et al., 2005; Towle et al., 2013 Peptides 85 Neopetrosiamdes A and B njaoamines G (23) and H (24) and 1,2,3,4-tetrahydroquinolin-4-one (25) were obtained from the sponge Neopetrosia sp. collected from Pemba Island, Tanzania (Sorek et al., 2007). A pentacyclic hydroquinone exiguaquinol was isolated from the methanol extract of the Australian sponge Neopetrosia exigua (Leone et al., 2008). Neopetrosiamine A (26) was extracted from the marine sponge Neopetrosia proxima collected off the west coast of Puerto Rico (Wei et al., 2010). Three xestoproxamines A (27), B (28) and C (29) were isolated from the Bahamian sponge N. proxima(Morinaka and Molinski, 2011). Pyridoacridine alkaloids Six pyridoacridine alkaloids have been reported from N. carbonaria collected from Palau including 1-hydroxydeoxyamphimedine (30), 3-hydroxy-deoxyamphimedine (31), debromopetrosamine (32), amphimedine (33), neoamphimedine (34) and deoxyamphimedine (35) (Wei et al., 2010). Others alkaloids Eight motuporamines including motuporamine A (36), B (37) and C (38) , D(39), E (40) and F (41) and a mixture of G, H, and I (42) were obtained from N. exigua (Xestospongia exigua) collected from Papua New Guinea yielded (Williams et al., 1998; Williams et al., 2002). Two phenethyl-guanidine derivatives, 7,8-dihydrotubastrine (43) and 4-deoxy-7,8-dihydrotubastrine (44), were isolated from the from the Indo-Pacific sponge N. contignata (Petrosia cf. contignata) (Sperry and Crews, 1998). Quinones More than 21 quinone and hydroquinone derivatives have been isolated from Neopetrosia genus. Several 440 Bangladesh J Pharmacol 2016; 11: 433-452 and demethylxestopongin B (19) were isolated from the Hainan sponge N. exigua (Li et al., 2011). soluble fraction of N. exigua (Haliclona exigua) (Dube et al., 2007). A bis-quinolizidine alkaloid, xestosin A (13), was isolated from the Papua New Guinean sponge N. exigua (Xestospongia exigua) (Iwagawa et al., 2000). Two bis-quinolizidine alkaloids namely, petrosin (14) and petrosin-A (15) were isolated from N. similis (Venkateshwar Goud et al., 2003). Three macrocyclic quinolizidines alkaloids were obtained from the nbutanol extract of N. exigua (Xestospongia exigua) collected in Palau including araguspongine M (16), araguspongines B (6) and D (1) (In 2004, Liu et al., 2004). 9'-Epi-3ß,3'ß–dimethylxestospongin C (17), xestospongin A (1), 3ß,3'ß–dimethylxestospongin C (18) N H O HO O OH H CH3 N CH3 N CH3 H O H O H O H N H O O H O N H3C N H O HO H O H N N H3C 9'-epi-3beta,3'beta- Araguspongine M (16) Petrosin-A (15) H O OH N H3C CH3 N H O N H3C Petrosin (14) CH3 H O N H3C Xestosin A (13) Ten 3-alkylpyridine alkaloids were reported from Neopetrosia genus. Renieramycin J (20), a tetrahydroisoquinoline alkaloid, was reported from Neopetrosia sp. collected from Iwo-Jima Island, Japan (Oku et al., 2003). Renieramycin A (21) was reported from the Japanese sponge Neopetrosia sp. (Nakao et al., 2004). A hexacyclic alkaloid, exiguamine A (22), was isolated from Neopetrosia exigua collected in Papua New Guinea (Brastianos et al., 2006). Two polycyclic alkaloids, N O N 3-Alkylpyridine alkaloids Dimethylxestospongin B (19) 3beta,3'beta- Dimethylxestospongin C (17) Dimethylxestospongin C (18) O HO O O O H H CH3 OH H3C H Renieramycin A (21) O H O O O OH NH2 S O CH3 CH3 O O H O Renieramycin J (20) O N H HO O O N HO OH N R O Exiguamine A (22) CH3 OH N O OH CH3 O N OH N H O H N CH3 O CH3 H H3C H3C O CH3 S O S Njaoamines G (23), R=H Njaoamines H (24), R=OH N 441 Bangladesh J Pharmacol 2016; 11: 433-452 O H H H H N N H N H H H N N H 1,2,3,4-Tetrahydroquinolin-4pne (25) Neopetrosiamines A (26) Xestoproxamines A (27) H H H N H N H H H H N Xestoproxamines B (28) N CH3 Xestoproxamines C (29) HO OH N N N O + N + N H3C N O N H3C + N H N O H O 1-Hydroxy-deoxyamphimedine (30) 3-Hydroxy-deoxyamphimedine (31) Debromopetrosamine (32) N N N H O + N N N N H O Amphimedine (33) H N O O O Neoamphimedine (34) polycyclic quinones and hydroquinones compounds were isolated from N. Carbonaria including tetrahydrohalenaquinone A (45), tetrahydrohalenaquinone B (46), 14-methoxyhalenaquinone (47), halenquinone (48), halenquinol (49), halenquinol sulfate (50), xestoquinone (51), xestoquinolide A (52) and xestoquinolide B (53) (Alvi et al., 1993). Halenaquinone (48) was obtained from N. exigua (Xestospongia exigua) benzene extract (Roll et al., 1983). Halenaquinol (49) was reported from N. Sapra (Kobayashi et al., 1985) and N. seriata (Petrosia seriata) (Gorshkova et al., 1999). Halenaquinol sulfate (also called xestoquinol sulfate) (50) was isolated from Okinawan sponge N. Sapra (Kobayashi et al., 1985; Kobayashi et al., 1992). Two other hydroquinones were isolated from Okinawan marine sponge N. sapra namely xestosaprols A (54) and B (55) (Kubota et al., 2008). Xestosaprol C (56), a pentacyclic hydroquinone sulfate, was obtained from an Okinawan marine sponge N. sapra (Kubota et al, 2008). Two sesquiterpene benzoquinones neopetrosiquinones A (57) and B (58), were reported from the ethanol extract of N. Proxima N H Deoxyamphimedine (35) (Winder et al., 2011). 1, 2-dihydroisoquinoline (59) and isoquinoline-quinone (60) were obtained from the sponge N. similis (Petrosia similis) (Ramesh et al., 1999). Sterols 14 sterols compounds were isolated from Neopetrosia genus. Seven sterols derivatives were obtained from the n-butanol extract of N. exigua (Xestospongia exigua) collected in Palau including three galactosyl diacylglycerols (61, 62, 63), 24-methyl cholesterol (64), 5, 6-dihydrocholesterol (65), -sitosterol (66), and three 5 , 8 -epidioxy sterols (67, 68, 69). 5 , 8 -epidioxy sterol, 5 , 8 -epidioxy-24 -ethylcholest-6-en-3-ol (70), and clionasterol (71), clionasterol monoacetate (72) and sitosterol (66) were reported from N. exigua (Xestospongia exigua) (Cerqueira et al., 2003). The sterol xestobergsterol A (73), was isolated from N. contignata (Petrosia cf. contignata) (Sperry and Crews, 1998). Terpenoids Twelve terpenoids were found in Neopetrosia genus. 442 Bangladesh J Pharmacol 2016; 11: 433-452 NH NH2 N N Motuporamines A (36) N NH2 Motuporamines B (37) N NH NH2 Motuporamines C (38) N NH NH NH2 Motuporamines D (39) NH NH2 Motuporamines E (40) N Motuporamines F (41) NH NH H O CH3 H NH NH2 N Motuporamines G, H, I (42) Two triterpene glycosides, xestovanin A (74) and secoxestovanin A (75) were reported from the Northeastern Pacific sponge N. vanilla (X. vanilla) (Northcote and Andersen, 1989; Andersen et al., 1988). Isoxestovanin A (76), Xestovanins B (77), C (78) and dehydroxestovanin C (79) were obtained from the Northeastern Pacific species of N. vanilla (Xestospongia vanilla) (Morriset al., 1991). Xestodiol (80), Xestenone (81), Xestolide (82), secoxestenone (83), and secodehydroxestovanine A (84) were isolated from N. Vanilla (Northcote and Andersen, 1987; Northcote and Andersen, 1989; Morriset al., 1991). Peptides Only two diastereomeric tricyclic peptides, neopetrosiamdes A and B (85), which differ only by the stereochemistry of the sulfoxide group, were isolated from Neopetrosia sp. collected in Papua New Guinea (Williams et al., 2005; Towle et al., 2013). Biological activities Antimicrobial, antifouling and anti-HIV activities The in vitro antimicrobial and antifouling activities of Neopetrosia extracts have been confirmed. In screening of invertebrate materials for antifouling activity, MoraCristancho and co-authors (2011) identified the CH2Cl2/MeOH extract of N.carbonaria as a potent antimicrobial extract against the fouling bacterial strains Oceanobacillus iheyensis, Kocuria sp., Vibrio harveyi and Bacillus megaterium with more than 12 mm inhibition zone (300 µg extract concentration) (MoraCristancho et al., 2011). Aqueous and organic extracts from N. exigua exhibited stronger antibacterial and antifungal activities. The highest activity was obtained for the aqueous extract against the Gram-positive bacteria B. cereus (inhibition zone 25 mm and MIC 0.07 mg/mL) and S. aureus (17.5 mm and 0.12 mg/mL) and against C. albicans (21 mm and 0.32 mg/mL) (Qaralleh et al., 2010; Majali et al., 2015). The methanol extract of the marine sponge N. exigua (Haliclona exigua) was tested in micro-dilution method and indicated significant antifungal activity in vitro against Candida albicans (MIC = 7.8 µg/mL), Cryptococcus neoformans (MIC = 31.2 µg/mL), Sporothrix schenckii (MIC = 31.2 µg/mL), Trichophyton mentagrophytes (MIC = 31.2 µg/ mL), Aspergillus fumigatus (MIC = 31.2 µg/mL) and Candida parapsilosis (MIC = 7.8 µg/mL) (Lakshmi et al., 2010). The extract provided one active compound 443 Bangladesh J Pharmacol 2016; 11: 433-452 O NH2 NH2 NH2 N N OH NH2 H O HO H O HO 7,8-Dihydrotubastrine (43) 4-Deoxy-7,8-dihydrotubastrine (44) Tetrahydrohalenquinone A (45) HO O O O O H H O HO O O O O O O O Tetrahydrohalenquinone B (46) 14-Methoxyhalenquinone (47) R Halenquinone (48) O O OH O H O O O O O H3C O Halenquinol (49), R= OH O CH3 H O H O H H CH3 O Xestoquinolide A (52) Xestoquinone (51), R=H Halenquinol sulfate (50), R= SO 3Na or Xestoquinol sulfate X Y O R + OH 1 H3C O OSO3H H H3C OH O CH3 O R H3C O O 2 O Xestosaprols A (54), R1=H,OH R2=O OH O O OH Xestosaprols C (56) Xestosaprols B (55), R1=R2=H,OH Xestoquinolide B (53) X= NH, Y=SO2 or X=SO2, Y=NH namely araguspongin C (7), that showed promising activity against Cryptococcus neoformans, Sporothrix schenckii, Trichophyton mentagrophytes and Aspergillus fumigatus with identical MIC of 50 µg/mL. In another study, araguspongin C (7) isolated from N. exigua exhibited potent antifouling activity with EC50 = 6.6 µg/mL and low toxicity with LC50 = 18 µg/mL (Limna Mol et al., 2009; Limna Mol et al., 2010). In a screening of crude extracts of 6 species of sponges for their antifouling activity, Limna Mol and co-authors (2010)reported the methanol/acetone extract of the N. exigua as a moderate antifouling extract. N. exigua extract exhibited moderate antibacterial activity against the fouling bacterial strains; Bacillus cereus; B. pumilus; B. megaterium; Pseudoalteromonas haloplanktis; Pseudomonas chlororaphis; P. putida; P. aeruginosa. In a preliminary screening study, the chloroform and methanol extracts of N. proxima collected from the Uraba Gulf in the Colombian Caribbean region, showed no antibacterial activity against Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922 and antifungal activity against Candida albicans ATCC 10231 (Galeano and Martínez, 2007). In contrast, the organic extract obtained from N. proxima showed in vitro antibacterial activity against the Gram-positive Staphylococcus aureus and Streptococcus faecalis and antifungal activity against Candida albicans (Mora et al., 2008). A pentacyclic polyketide, halenaquinone (48) isolated from the benzene extract of N. exigua (Xestospongia 444 Bangladesh J Pharmacol 2016; 11: 433-452 O O OH O O H H N MeO O H OAc H H O H HO 1,2-Dihydroisoquinoline (59) H Neopetrosiquinones A (57) HOOR CHO Isoquinolinequinone (60) Neopetrosiquinones B (58) 2 CH3 CH3 H3C HO O CH3 CH3 O OH H 1 OR1 OR CH3 Galactosyl diacylglycerol HO R1=16:0\16:1 R2=H (61) 24-Methylcholestrol (64) R1=16:0\18:2 R2=H (62) R1=16:0\16:1 R2= alpha-D-galactopyranosyl (63) α CH3 CH3 H3C CH3 H3C CH3 CH3 CH3 CH3 CH3 CH3 HO HO Beta-sitosterol (66) 5,6-Dihydroxycholestrol (65) CH3 CH3 CH3 CH3 CH3 H3C CH3 CH3 H CH3 CH3 H CH3 CH3 O HO CH3 H3C O HO O O 5Alpha,8alpha-epidioxy sterol (67) 5Alpha,8alpha-epidioxy sterol (68) CH3 H3C CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 O HO CH3 H3C O 5Alpha,8alpha-epidioxy sterol (69) O HO O 5Alpha,8alpha-epidioxy-24alpha -ethylcholestrol-6-en-3-ol (70) 445 Bangladesh J Pharmacol 2016; 11: 433-452 CH3 H3C CH3 H3C CH3 H3C CH3 CH3 CH3 CH3 O HO HO Clionasterol (71) H CH3 CH3 H H O Clionasterol monoacetate (72) HO CH3 CH3 H CH3 H H HO OH H H O CH3 H HO CH3 Xestobergsterol A (73) exigua) was reported with antibacterial activity against Staphylococcus aureus and Bacillus subtilis (Roll et al., 1983). (+)-Araguspongine C (7) was reported with antituberculosis activity with MIC 3.9 µM (Orabi et al., 2002). The anti-tuberculosis activity was confirmed for neopetrosiamine A (26) in vitro against a pathogenic strain of Mycobacterium tuberculosis (H37Rv) with MIC value of 7.5 µg/mL (Weiet al., 2010). A pentacyclic hydroquinone exiguaquinol inhibited Helicobacter pylori glutamate racemase (MurI) with an IC50 of 4.4 µM. The triterpene glycosides, xestovanin A was reported from N. vanilla with antifungal activity against Phytium ultimum (Northcote and Andersen, 1989). Two bis-quinolizidine alkaloids namely, petrosin (14) and petrosin-A (15) were reported as anti-HIV inhibitors with IC50 values of 41.3 and 52.9 μm, respectively (Venkateshwar et al., 2003). Cytotoxic, antitumor, anti-proliferation, anti-angiogenic and anti-invasion activities Selective cytotoxic activity was indicated for N. contignata extract against tumor cell lines HT-29, T47D and Casky with IC50 of 78.9, 35.6 and 36.2 µg/mL, respectively (Abdillah et al., 2013a). Using BST test, the hydro-ethanolic extract of N. contignata and N. exigua (X. exigua) exhibited strong toxicity with LC50 equal to 155 and 547 ppm, respectively. The pyridoacridine alkaloids, amphimedine (33) isolated from N. carbonaria exhibited potent cytotoxic activity that caused a phenotype in zebra fish embryos at 30 µM (Wei et al., 2010). In 2004, Liu and colleagues (2004) reported the cytotoxic activities of araguspongine M (16), araguspongines B (6) and D (1) and three 5 , 8 epidioxy sterols (67–69) against the human leukemia cell line HL-60 with IC50 values of 5.5, 5.5, 5.9, 22.4, 9.5, and 9.6 µM, respectively. Renieramycin A (21) obtained from Neopetrosia sp. exhibited cytotoxicity with IC50= 2.2 μg/mL. Renieramycin J (20) was reported with cytotoxic activity against 3Y1, HeLa, and P388 cells with IC50 of 5.3, 12.3, and 0.53 nM, respectively (Oku et al., 2003). High concentration of renieramycin J induced morphological changes in 3Y1 cells in which these changes might be refer to RNA and/or protein synthesis inhibition. Sorek and co-authors (2007) reported that njaoamines G (23) and H (24) possess potent brine shrimp toxicity with LD50 values of 0.17 and 0.08 µg/mL, respectively. Demethylxestopongin B (19) was isolated from the Hainan sponge N. exigua as a potent cytotoxic compound against human tumor cell line A-549 with inhibition ratio of 94.3% at 10 µM (Liet al., 2011). Halenaquinone (48) was found to exhibit anticancer activity through apoptosis. Fujiwara and co-authors (2001) reported that the mechanism of halenaquinoneinduced apoptosis may be explained by the inhibition of phosphatidylinositol 3-kinase activity. Winder and colleagues (2011) reported the antiproliferation activity of neopetrosiquinones A (57) and B (58) against the DLD-1 human colorectal adenocarcinoma cell line with IC50 values of 3.7 and 9.8 µM, respectively and the PANC-1 human pancreatic carcinoma cell line with IC50 values of 6.1 and 13.8 µM, respectively. Neopetrosiquinone A (57) also inhibited the in vitro proliferation of the AsPC-1 human pancreatic carcinoma cell line with an IC50 value of 6.1 µM. 446 Bangladesh J Pharmacol 2016; 11: 433-452 Alpha-L-Rhap OH CH3 O OH CH3 O Alpha-L-Rhap OH OH CH3 HO O H3C OH OH O OH Beta-D-Fucp O H3C OH CH3 HO O H3C CH3 H H3C CH3 CH3 H O H3C CH3 O O H3C OH CH3 O OH Beta-D-Fucp CH3 CH3 CH3 O CH3 CH3 HO Secoxestovanin A (75) Xestovanin A (74) Alpha-L-Rhap CH3 OH O HO Alpha-L-Rhap O OH CH3 CH3 O HO O OH HO OH OH CH3 H O CH3 H3C OH CH3 O HO O H3C CH3 O OH Beta-D-Fucp CH3 O CH3 H3C OH Beta-D-Fucp CH3 H CH3 HO CH3 O Isoxestovanin A (76) H3C CH3 OH H3C HO Alpha-L-Rhap O OH CH3 O O OH O OH Beta-D-Fucp CH3 HO O H3C O H3C OH CH3 CH3 O O OH CH3 Xestovanin B (77) OH CH3 Alpha-L-Rhap CH3 Alpha-L-Rhap O OH OH OH CH3 O Alpha-L-Rhap OH CH3 OH OH O OH O OH Beta-D-Fucp CH3 HO O H3C O CH3 H3C CH3 H OH CH3 H Xestovanin C (78) CH3 O H3C CH3 CH3 CH3 O H3C HO CH3 CH3 HO Dehydroxestovanin C (79) In vitro anti-tumor screening showed that neopetrosiamine A (26) exhibited strong inhibitory activity against MALME-3M melanoma cancer, CCRFCEM leukemia and MCF7 breast cancer with IC values of 1.5, 2.0, and 3.5 µM, respectively. Notably, neopetrosiamine A did not exhibit cytotoxicity against VERO cells (IC50 = 42.4 µg/mL). showed that the compound motuporamine C (38) interferes with the migration of human breast carcinoma, prostate carcinoma and glioma cells in culture and inhibited angiogenesis in both an in vitro sprouting assay and an in vivo chick chorioallantoic membrane assay (Williams et al., 1998; Roskelley et al., 2001; Williams et al., 2002). Motuporamines A (36), B (37) and C (38) and the mixture of G, H and I (42) exhibited anti-invasion activity. In 2001, Roskelley and colleagues (2001) Neopetrosiamdes A and B (85) were reported as potential anti-metastatic agents that inhibit tumour cell invasion by both amoeboid and mesenchymal 447 Bangladesh J Pharmacol 2016; 11: 433-452 CH3 O O H3C CH3 H3C H3C CH3 CH3 CH3 H3C H H3C OH OH Xestenone (81) Xestodiol (80) OH O H3C CH3 H O O O HO O H3C H3C CH3 CH3 H3C CH3 H3C OH Secoxestenone (83) Xestolide (82) CH3 OH OH CH3 O OH OH CH3 HO O O H3C H3C O OH CH3 CH2 H O OH H3C CH3 O CH3 CH3 Secodehydroxestovanin A (84) Enzymes inhibitors Halenaquinol (49), isolated from N. seriata, was reported as inhibitor for rat brain cortex Na+, K+ ATPase with an I50 value of 1.3 x 10 - 6 M or 325 nmol per mg of protein (Gorshkova et al., 1999). Further investigation suggested that halenaquinol interacts with the essential sulfhydryls in or near the ATP-binding site of Na+, K+-ATPase. This interaction resulted in a change of protein conformation and subsequent alteration of overall and partial enzymatic reactions (Gorshkova et al., 2001). Exiguamine A (22), has been found to be one of the most potent inhibitor of indoleamine-2, 3-dioxygenase (IDO) in vitro. IDO inhibition can delay tumor growth (Brastianos et al., 2006). Araguspongines A (5) and C (7) showed an ability to inhibit rat brain nitric oxide synthase activity in vitro with an estimated IC50 of 31.5 and 46.5 mM respectively (Venkateswara et al., 1998). Halenaquinone (48) and 14-methoxyhalenaquinone (47) were reported as a potent protein tyrosine kinase (PTK) inhibitors with IC50 values <10 muM (Alvi et al., 1993). This enzyme is associated with proliferative disease such as cancer. Araguspongines A (5) and C (7) and xestospongin B (2) were reported as a potent inhibitors for inositol 1, 4, 5triphosphate receptor mediated Ca2+ release and endoplasmic reticulum-calcium pump (Gafni et al., 1997; De Smet et al., 1999). migration pathways (Williams et al., 2005; Towle et al., 2013). Anti-oxidant activity Anti-oxidant activities of N. contignata and N. exigua (Xestospongia exigua) extract were reported. The hydroethanolic extract of N. contignata and N. exigua exhibited moderate antioxidant activity with IC50 <100 µg/mL using DPPH method (Abdillah et al., 2013a). 448 Bangladesh J Pharmacol 2016; 11: 433-452 H3C NH2 O H2N O O NH N N H O CH3 O H N O NH O NH O N H CH3 S S O NH H3C H3C O O HN OH S HO H N CH + 3 HO S O H N NH CH3 NH S OH O HN CH2 O O O HN S O O HN N OH O O O O S O NH O O H N N H O HO CH3 N H O H N CH3 O N H H3C O NH H N N O HN Neopetrosiamides (85) HN Antiprotozoal activity Recently, the anti-malarial activity of N. exigua has been reported. Ethanol soluble extracts of N. exigua with doses of 400 and 200 mg/kg showed suppression of growth activity against Plasmodium berghei by 80.7% and 60.6%, respectively (Abdillah et al., 2013a). Neopetrosamine A (26) was reported with antiplasmodial activity against Plasmodium falciparum with an IC50 value of 2.3 µM (Wei et al., 2010). Renieramycin A (21) exhibited anti-protozoal activity against Leishmania amazonensis with IC50 = 0.2 μg/mL and cytotoxicity with IC50 = 2.2 μg/mL (Nakao et al., 2004). Araguspongine C (7) exhibited in vitro anti-malarial activity against Plasmodium falciparum with IC50 ranged from 280 to 670 ng/mL (Orabi et al., 2002). Anti-inflammatory activity and anti-complementary inhibitor The anti-inflammatory activity of N. proxima and N. rosariensis collected from the Colombian Caribbean has been confirmed. The methanolic extract and the different polarity fractions of N. Proxima exhibited in vitro and in vivo anti-inflammatory activities. Total extracts of N. proxima (100 mg/Kg) significantly inhibited the paw edema of rats (60%). Dichloro- NH2 methane and methanol fractions reduced myeloperoxidase activity (MPO) while there was no significant reduction for the nitric oxide (NO), prostaglandin E2 (PGE2) and tumor necrosis factor alpha (TNF- alpha) (Franco et al., 2012). Total extracts of N. rosariensis (100 mg/Kg) significantly inhibited the paw edema of rats (72%). Dichloromethane and methanol fractions reduced myeloperoxidase activity (MPO). Only, dichloromethane fraction of N. rosariensis significantly inhibited nitric oxide (NO) (66%), prostaglandin E2 (PGE2) (30.5%) and tumor necrosis factor alpha (TNF-alpha) production (72%) (Franco et al., 2012). Clionasterol (71), isolated from N. exigua (Xestospongia exigua), exhibited potent anticomplementary inhibitor with IC50 = 4.1 μM (Cerqueira et al., 2003). Other Xestospongin A (1), B (2), C (3) and D (4) were found to be active as a vasodilator compounds since they induce relaxation of blood vessel in vivo (Zhou et al., 2010). Halenaquinol (49) was reported from N. seriata with a cardioactivity (Gorshkova et al., 1999). Xestosaprol C (56) was reported with cardiotonic activity (Nakamura et al., 1985). Halenaquinone (48), was found to be as an inhibitor of osteoclastogenic differentiation of murine Bangladesh J Pharmacol 2016; 11: 433-452 RAW264 cells (Tsukamoto et al., 2014). Chemotaxonomic significance A literature search showed that only 9 species out of 27 of Neopetrosia that have been chemically investigated. In general, these species produced alkaloids, quinones, sterols and terpenoids. Macrocyclic quinolizidines are a major kind of metabolite that existed in this genus and more specifically in N. exigua and N. similis. Most other similar macrocyclic quinolizidines [(+)-araguspongine A-J] were reported from Xestospongia sp. that has been identified to the genus level(Kobayashi et al., 1989). In this study, 3-alkylpyridine alkaloids were found in N. exigua, N. proxima and Neopetrosia sp. The occurrence of 3-alkylpyridine alkaloids has been reported from other sponge genera including xestospongia, amphimedon and Topsentia suggested that these genera share similar biosynthetic pathways. Previous studies reported that Xestospongia wiedenmayeri and X. ingens contain 3alkylpyridine alkaloids such as xestamine and ingamine, respectively (Quirion et al., 1992; Kong and Andersen, 1995; Takekawa et al., 2006). In this review, six pyridoacridine alkaloids were reported from N. carbonaria. Previous reports showed that pyridoacridine alkaloids are produced by other marine sponge including Oceanapia sp. (Eder et al., 1998), Petrosia sp (Nukoolkarn et al., 2008) and from ascidian species such as Cystodytes dellechiajei (Torres et al., 2002) and Lissoclinum cf. Badium (Clement et al., 2008). About eight motuporamines (36-42) were found in N. exigua (Williams et al., 1998; Williams et al., 2002). The occurrence of motuporamines in N. exigua only could be considered as important marker for this species. Only two phenethylguanidine derivatives were found in Neopetrosia genus. These two compounds, 7, 8a nd 4 - d eo xy -7 ,8 d i hy dr o t u bas t r in e (43) dihydrotubastrine (44), were found in N. contignata (Petrosia cf. contignata) (Sperry and Crews, 1998). According to literatures, there are no phenethylguanidine derivatives with similar skeleton have been reported from marine origin. More than 21 quinone and hydroquinone derivatives have been isolated from Neopetrosia genus. These derivatives were found in N. carbonaria, N. exigua, N. sapra, N. proxima, N. seriata and N. similis. Many quinone and hydroquinone derivatives have been obtained from Xestospongia specimen that identified to the genus level (Zhu et al., 1998; Concepción et al., 1995). Xestoquinone and halenaquinone have been found in marine sponge Adocia sp (Schmitz and Bloor, 1988). In this study, 13 sterols compounds were found in N. exigua while one was obtained from N. contignata. Many of these sterols or others with similar skeleton have been reported from Xestospongia genus. Some of these 449 sterols appear to be widely distributed in other organisms such as marine sponge Spirastrella inconstans (Das et al., 1993) and green alga Halimeda macroloba (Dzeha et al., 2004). The only Neopetrosia sp that has been reported to produce terpenoids is N. vanilla. These terpenoids (74-79) might be used as a specific marker for this species. Conclusion Out of 27 species of the genus Neopetrosia only Neopetrosia carbonaria, Neopetrosia contignata, Neopetrosia exigua, Neopetrosia proxima, Neopetrosia rosariensis, Neopetrosia sapra, Neopetrosia seriata, Neopetrosia similis and Neopetrosia vanilla have been studied so far. Most species of Neopetrosia haven't been investigated yet for their secondary metabolite profiles and potential bioactivities, some of taxa mentioned in the literature have been assigned to a genus level. Accordingly, it is difficult to determine such compounds as chemosystematic markers for particular species in this genus. Beside, sponge metabolites could be synthesised by the sponge itself or it is obtained from other sources such as the symbiotic microbes or the free living microbes in the marine environment (Garson et al., 1992; Lindquist et al., 2005). Because only 9 out of 27 species of the genus Neopetrosia have been chemically studied thus far, there is significant opportunity to find out new chemical constituents from this genus. Acknowledgement The author is thankful to the Department of Medical Support, Al-Balqa Applied University, Al-Karak University College (AlKarak, Jordan) for providing some technical facilities to accomplish this study. References Abdillah S, Nurhayati APD, Nurhatika S, Setiawan E, Heffen WL. Cytotoxic and anti-oxidant activities of marine sponge diversity at Pecaron Bay Pasir Putih Situbondo East Java, Indonesia. J Pharm Res. 2013a; 6: 685-89. Abdillah S, Wahida Ahmad R, Kamal Muzaki F, Mohd Noor N. Anti-malarial activity of Neopetrosia exigua extract in mice. J Pharm Res. 2013b; 6: 799-803. Alvi KA, Rodriguez J, Diaz MC, Moretti R, Wilhelm RS, Lee RH, Slate DL, et al. 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