(family Hymedesmiidae) collected from the Red Sea coast in 1989, renewable efforts led to the discovery of further crambescidin analogues. genus (family Chondropsidae) to other genera like and (family Crambeidae). A chemosystematic exploration has revealed that sponges containing cyclic guanidine alkaloids are chemically and taxonomically similar, and perhaps synonymous with, and sponges produced pyrroloquinoline alkaloids is taxonomically unrelated to the previously mentioned. Chemically, it is almost similar to the and marine sponges but their phylogenetic relationship is still undetermined . Systematically, the World Porifera Database accepts nine valid species of , nine valid species VER-50589 in the genus  and fourteen valid species currently in the genus . To the best of our knowledge, previous chemical investigations of was centered on only a single unidentified species from Madagascar , for the genus only one identified species, the type species from the Mediterranean  and finally five identified species including , , ,  and  in addition to one unidentified species of n. sp. . 2. Chemistry and Biology of Natural Products Isolated from and sp. and represented the first naturally occurring marine iminosugars. These compounds demonstrated inhibition of the growth of with MICs (Minimum Inhibitory Concentration) that were under 6.3 M  (Figure 1). Open in a separate window Figure 1 Isolated iminosugars 1C3 from sp. 2.2. Bicyclic Guanidine Alkaloids Eleven bicyclic guanidine metabolites including five bearing crambescin type A (4C8), three bearing crambescin type B (9C11) and further three possessing crambescin type C (12C14) were recorded from the Mediterranean sponge sp. Compound 15 displayed potent cytotoxicity against proliferating Vero cells and HIV gp120-human CD4 binding inhibition VER-50589 activity with IC50 100 M . Further bicyclic compounds including dehydrocrambine A (16) recorded from sp. that inhibits HIV-1 fusion . Monanchorin (17), a guanidine alkaloid with unusual bicyclic skeleton from showed very weak cytotoxic activity VER-50589 with IC50 = 11.3 M against IC2 murine mast cell lines . The simple pyrimidine monalidine A (18), an anti-parasitic bicyclic PCPTP1 guanidine alkaloid, was recently recorded from . Urupocidins A (19) and B (20), bisguanidine alkaloids possessing unusual n. sp. including three bicyclic architectures possessing a free carboxylic acid group monanchoradins ACC (21C23) and four bicyclic compounds bearing crambescin A2 type skeleton with a short butyl-guanidine side chain including dehydrocrambescin A2 418 (24), (?)-crambescin A2 392 (25), (?)-crambescin A2 406 (26) and (?)-crambescin A2 420 (27) along with monalidine A (18). Most of these compounds showed antiproliferative and cytotoxic activities against several cancer cell lines including KB, HCT-116, HL-60, MRC-5 and B16-F10, with IC50 values in the micromolar range. The bicyclic analogue monanchoradin A (21) that bearing a carboxylic acid functionality was found to be less potent, however, it is still in the nanomolar range. On the other hand, the bicyclic compounds 24C27 bearing the butyl-guanidine terminus were found more potent, in particular (?)-crambescin A2 420 (27) that was found to be the most active with IC50 = 0.03 M against KB cancer cell lines . Moreover, the simple compound 18 showed potent antiproliferative and cytotoxic activities against KB, HCT-116, MDA-435, HL-60 and MRC-5 with an IC50 values 0.2/0.4, 0.84/0.74, 0.32/0.86, 1.3/1.3, 0.55/0.60 M respectively. It is worth noting that the bicyclic (?)-crambescin compounds 25C27 are enantiomers for the antipodal bicyclic (+)-crambescins, recently isolated from the marine sponge (now known as sp. . (+)-Ptilocaulin (32), an antimicrobial and cytotoxic tricyclic guanidine alkaloid, in addition to isoptilocaulin (33) and (+)-8-hydroxyptilocaulin (34), were obtained from [38,47]. Moreover, (+)-ptilocaulin (32), exhibited antimicrobial activity against.