**7. Marine sponge-derived compounds with enzyme inhibitory activity**

Derivatives of halenaquinone and xestoquinone showed various enzyme inhibitory activities besides the phosphatidylinositol 3-kinase and topoisomerase I and II inhibitory activities mentioned above. Compound xestoquinone inhibited both Ca2+ and K<sup>+</sup> -ATPase of skeletal muscle myosin [185]. SAR Investigations showed that halenaquinone and three synthetic analogs with a quinone structure significantly inhibited Ca2+ ATPase activity. In contrast, four xestoquinone


immunomodulatory potential. The immunomodulatory potential was evaluated by oral administration of ethyl acetate extract of marine sponge (200 mg/kg) to Wistar rats and the results obtained showed that extracts exhibited immunosuppressant activity and can further be studied [197]. A recent investigation on an Indian marine sponge aimed to isolate and characterize bacteria with immunomodulatory and antimicrobial activity. *Callyspongia difusa* (Gulf of Mannar province) a marine sponge resulted in isolation of 10 marine bacterial strains which exhibited remarkable antagonistic activity against clinical bacterial pathogens. These findings suggested that the sponge associated bacterial strain *Virgibacillus* sp. can contribute the search for novel antibiotics to overcome infections and also for the production of potential immunomodulators [109].

Biological and Medicinal Importance of Sponge http://dx.doi.org/10.5772/intechopen.73529 213

In the last decade studies reported that marine sponges could have been a source of hypocholesterolemic compounds. For example, lysophosphatidylcholines and lyso-PAF analogs derived from *Spirastrella abata* are reported as successful inhibitors of cholesterol biosynthesis in vitro study [198, 199]. Zhao et al. [200] extracted novel lysophosphatidylcholines from marine sponges with hypocholesterolemic properties and thereby aroused an interest of compounds from marine sponge due to short lifespan of conventional lysophosphatidylcholines *in vivo*.

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

**9. Hypocholesterolemic compounds**

**10. Sponge–derived antibiotics**

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

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**.

#### **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 immunomodulatory potential. The immunomodulatory potential was evaluated by oral administration of ethyl acetate extract of marine sponge (200 mg/kg) to Wistar rats and the results obtained showed that extracts exhibited immunosuppressant activity and can further be studied [197]. A recent investigation on an Indian marine sponge aimed to isolate and characterize bacteria with immunomodulatory and antimicrobial activity. *Callyspongia difusa* (Gulf of Mannar province) a marine sponge resulted in isolation of 10 marine bacterial strains which exhibited remarkable antagonistic activity against clinical bacterial pathogens. These findings suggested that the sponge associated bacterial strain *Virgibacillus* sp. can contribute the search for novel antibiotics to overcome infections and also for the production of potential immunomodulators [109].
