Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmacognosy

Two new cyclic heptapeptides P2: cyclo (l-Tyr-l-Pro-l-Ser-l-Leu-l-Tyr-l-Pro-l-Tyr) and P3: cyclo-(l-Pro-l-Phe-l-Ile-l-Pro-l-Pro-l-Glu-l-Tyr) were isolated from the bioactive extract of marine sponge Stylissa carteri along with three known cyclic heptapeptides, phakellistatin 13 (3) and hymenamides cand D and nine known pyrrole alkaloids, aldisine, 2-bromoaldisine, 2,3-dibromoaldisine, 4-bromopyrrole-2-carbamide, 4,5 dibromopyrrole-2-carbamide, latonduine B ethyl ester, monobromo-dispacamide, dispacamide and stevensin. Their structures were elucidated based on data obtained using 2D NMR, HRESIMS, and ESIMS/MS, in addition to Marfey{u2019}s analysis. P3 showed cytotoxicities strong against HeLa, HCT116, and RAW264 cells with IC50 values of 0.70-1.5 {uF06D}M while compounds hymenamides C and stevensin were moderately cytotoxic against HeLa (IC50, 25, 13{uF06D}M), and HCT116 (IC50, 5, 16{uF06D}M) cell lines. Phakellistatin 13, 4,5 dibromopyrrole-2-carbamide and latonduine B ethyl ester were only moderately cytotxic against HeLa cell lines (IC50, 15, 18, 15 {uF06D}M). Moreover, compounds S6 and S9 exhibited strong inhibition activity against Ubc13/Uev1A interaction (84% and 73% inhibition at 5 {uF06D}g/ml, respectively), and compound S9 exhibited moderate proteasome inhibition activity (61% inhibition at 5 {uF06D}g/ml) while the other compounds didn{u2019}t show any significant cytotoxic nor ubiquitin-proteasome inhibition

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