Discovery of cytotoxic natural products from Red Sea sponges: Structure and synthesis

Marine ecosystem continues to produce a great wealth of molecules endowed with cytotoxic activity towards a large panel of tumor cells. Marine sponges, apparently defenseless organisms are endowed through evolution with a range of cytotoxic metabolites for self protection against predators and space competition. Interestingly, high biodiversity of sponges with Demospongiae and Calcarea species that have yielded numerous bioactive compounds have been accorded in different regions of the Red Sea. This review for the first time provides a comprehensive overview of 123 cytotoxic agents derived from Red Sea sponges with diverse chemical structures covered till mid 2020 showing activities ranging from mildly active to very active against different panels of cancer cell lines. It has been divided according to the different classes of compounds including alkaloids, terpenoids (sesquiterpenes, diterpenes, triterpenes, sesterterpenes, norsesterterpenes), peptides and macrolides, lipids (steroids, fatty acids/amides and glycerides) etc. The enhancement in the cytotoxicity with respect to the molecular structure changes have been described in detail. We have also accounted for the total synthesis of cytotoxic molecules, subereamolline A, aerothionin, asmarine B, norrsolide and latrunculin B showing interesting activity against different cancer cell lines.