**10. Sponge–derived antibiotics**

analogs in which the quinine structure was converted to quinol dimethyl ether did not inhibit the Ca2+ ATPase activity [186]. The protein tyrosine kinase (PTK) inhibitory activities of halenaquinone, halenaquinol, and 14-methoxyhalenaquinone were the most remarkable with IC<sup>50</sup> values <10 mm. The other analogs was either less potent or inactive, and a rationalization for this SAR pattern was also reported [187]. Xestoquinone also showed significant protein kinase inhibitory activity toward Pfnek-1, a serine/threonine malarial kinase, with an IC<sup>50</sup> value of ca. 1 mm, and moderate activity toward PfPK5, a member of the cyclin-dependent kinase (CDK) family [188]. Adociaquinone B and 3-ketoadociaquinone B were the most potent inhibitors of the Cdc25 B phosphatase inhibitory activities, and the dihydro-benzothiazine dioxide in compounds Adociaquinone A, Adociaquinone B, 3-Ketoadociaquinone A, and 3-Ketoadociaquinone B appeared to be an important structural feature for this enhanced activity. Four cyclostellettamines, cyclostellettamine A, cyclostellettamine G, dehydrocyclostellettamine D and dehydrocyclostellettamine E inhibited histone deacetylase derived from K562 human leukemia cells with IC50 values ranging from 17 to 80 mm [189]. Xestospongic acid ethyl ester (207) was found to inhibit the Na+/K+ ATPase [190]. Compounds are listed in **Table 6**.

**Categories Species Active agents Enzyme-inhibitory References** Quinones *X. exigua* Halenaquinone Ca2+ ATPase activity [191]

> *X. sapra* Halenaquinol Protein tyrosine kinase activity [193] *X. cf. carbonaria* 14-Methoxyhalenaquinone Protein tyrosine kinase activity [187] *Xestospongia* sp. Adociaquinone B Protein tyrosine kinase activity [194] *Xestospongia* sp. 3-Ketoadociaquinone B Cdc25B phosphatase activity [195] *Xestospongia* sp. Adociaquinone A Cdc25B phosphatase [194] *Xestospongia* sp. 3-Ketoadociaquinone Cdc25B phosphatase [195]

> > Dehydrocyclostellettamine E [189]


*X. exigua* Xestoquinone Ca2+ and K<sup>+</sup>

212 Biological Resources of Water

Cyclostellettamines *Xestospongia* sp. Cyclostellettamine A histone deacetylase derived inhibition Cyclostellettamine G Dehydrocyclostellettamine D

**Table 6.** Marine sponge-derived compounds showing enzyme-inhibitory activities.

Fatty acids *X. testudinaria* Xestospongic acid ethyl ester inhibit the Na+/K+ ATPase [190]

**8. Sponge-derived immunosuppressive compounds and their efficacy**

Recently natural constituents isolated from marine sponges were tested for immunosuppressive activities and in the end of 1980s, deep water marine sponges resulted in isolation of pure compounds with immunosuppressive properties. Two important compounds: 4a-merhyl-5acholest-8-en-3~-ol and 4,5-dibromo-2-pyrrolic acid discovered by American scientist from deep water sponge *Agelasfla bellrform is* showed significant immunosuppressive activity. Both compounds were found significantly active in suppression of the response of murine splenocytes in the two-way mixed lymphocyte reaction (MLR) with little to no demonstrable cytotoxicity at low doses [196]. Constituents isolated from the Aurora globostellata marine sponge showed Also, over the years marine sponges are considered as a rich source of natural products and metabolites for antibiotics possessing strong inhibitory against bacteria, fungi and microbes. Several studies revealed that many natural bioactive components isolated from various marine sponges can be useful for the production of new antibiotics and antimicrobial drugs. In the recent years many scientific studies provided evidences for marine sponge metabolites with efficient antibiotic, antibacterials and antimicrobial properties. Purpuroines A-J, halogenated alkaloids isolated from *Lotrochota purpurea* marine sponge showed promising inhibitory activities against bacteria and fungi related diseases [201]. *Haliclona* sp. sponge from Korea resulted in isolation of novel cyclic bis-1,3-dialkylpyridiniums and cyclostellettamines, which showed moderate cytotoxic and antibacterial activities against A549 cell-line and Gram-positive strains, respectively [202]. A number of new alkaloids were isolated from the marine sponge *Agelas mauritiana*: (+)-2-oxo-agela-sidine C, (−)-8′-oxo-agelasine D,4-bromo-N-(butoxymethyl)-1Hpyrrole-2-carboxamide, ageloxime B, and (−)-ageloxime D and some of these isolated components exhibited antifungal activity against *Cryptococcus neoformans*, antileishmanial activity in vitro and antibacterial activity against *S. aureus* and methicillin-resistant *S. aureus in vitro* [203]. Extracts prepared from the sponge's species *Petromica citrina*, *Haliclona* sp. and *Cinachyrella* sp. exhibited antibacterial activity against 61% of the coagulase-negative staphylococci (CNS) strains, including strains resistant to conventional antibiotics. *P. citrina* extracts showed the largest spectrum of inhibitory activity. This current study according scientist shows potential of marine sponges to become new sources of antibiotics and disinfectants for the control of CNS involved in bovine mastitis in future [204]. Isolation of isonitriles ditepene from *Cymbastela hooperi*, tropical marine sponge and the axisonitrile-3 sesquiterpene isolated *Acanthella kletra*, from the tropical marine sponge were tested for series of bioassays antibacterial, antiphotosynthetic, antifouling, antialgal, antifouling, antialgal, antiphotosynthetic, antifungal, and antitubercular. The results showed majority of the tested compounds were active against at least two of the applied test systems [152]. Recently, sponge-derived actinomycetes and sediments isolated from marine sponge were tested for bioactive constituents with antifungal and antimicrobial activity. Out of 15 prepared active extract nine were found active against *Enterococcus fascism* (vancomycin-resistant) and *Candida albicans* multidrug-resistant [132], including strains resistant to conventional antibiotics. Thus the bacterial actinomycetes from marine sponges and other marine organisms have been proved prolific producers of pharmacologically active compounds. Literature studies revealed that 70% of naturally derived antibiotics which are currently in clinical use have been derived from actinomycetes. In the recent study, *Streptomyces* sp. strains from Mediterranean sponges and secondary metabolite namely, cyclic depsipeptide valinomycin, indolocarbazole alkaloid staurosporine and butenolide, were screened for anti-infective activities. All the isolated compounds along with *Streptomyces* sp. exhibited antiparasitic activities. Researchers also claim the anti-infective potential of marine actinomycetes is very promising.

possesses vast range of therapeutic application, including antimicrobial, antihypertensive, antioxidant, anticancer, anticoagulant, anti-inflammatory, immune modulator, and wound healing and other medicinal effects. Therefore, marine sponges are considered a rich source of chemical diversity and health benefits for developing drug candidates, nutritional supplements, cosmetics, and molecular probes that can be supported to increase the healthy life span of humans. In this chapter we included the most important and biologically active marine sponge-derived compounds and presented selected studies of most important bioactive and promising natural products and sec-

Biological and Medicinal Importance of Sponge http://dx.doi.org/10.5772/intechopen.73529 215

ondary metabolites from marine sponges.

Musarat Amina\* and Nawal M. Al Musayeib

maceutics. 2007;**3**:275-279

2014;**12**:4539-4577

2007;**71**:295-347

The authors declare that they have no conflict of interest.

\*Address all correspondence to: musarat.org@gmail.com

ation—A review. Marine Drugs. 2010;**8**:1417-1468

ducts Chemistry and Research. 2013;**1**:1-8

Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh,

[1] Hentschel U, Schmid M, Wagner M, Fieseler L, Gernert C, Hacker J. Isolation and phylogenetic analysis of bacteria with antimicrobial activities from the Mediterranean sponges *Aplysina aerophoba* and *Aplysina cavernicola*. FEMS Microbiology Ecology. 2001;**35**:305-312

[2] Radjasa OK, Sabdono A, Junaidi, Zocchi E. Richness of secondary metabolite-producing marine bacteria associated with sponge *Haliclona* sp. International Journal of Phar-

[3] Thomas TR, Kavlekar DP, LokaBharathi PA. Marine drugs from sponge-microbe associ-

[4] Perdicaris S, Vlachogianni T, Valavanidis A. Bioactive natural substances from marine sponges: New developments and prospects for future pharmaceuticals. Natural Pro-

[5] Mehbub MF, Lei J, Franco C, Zhang W. Marine sponge derived natural products between 2001 and 2010: Trends and opportunities for discovery of bioactive. Marine Drugs.

[6] Taylor MW, Radax R, Steger D, Wagner M.Sponge-associated microorganisms: Evolution, ecology, and biotechnological potential. Microbiology and Molecular Biology Reviews.

**Conflict of interest**

**Author details**

Saudi Arabia

**References**
