Design and synthesis of cenocladamide analogues and their evaluation against breast cancer cell lines12. Issue 4 (12th December 2016) - Santos, Carla C. F.
Abstract : Synthesis of a concise series based on the natural product cenocladamide, their evaluation against a panel of breast cancer cells and preliminary mechanistic studies are discussed in this work. Abstract : This work describes the total synthesis of the alkaloid cenocladamide and a concise library of nine structural analogues aiming at their evaluation against the breast cancer cell line MDA-MB-231. The most promising compound (3 ; IC50 = 6.6 μM) was also evaluated in a panel of seven breast cancer cell lines and two non-tumorigenic cell lines. We further conducted an initial investigation on the mechanism of action of analogue3, which lacks the endocyclic double bond when compared to cenocladamide. The present study presents the discovery of a cenocladamide analogue with interesting cytotoxic activity, which could be useful for further optimization towards new chemotherapeutic agents for breast cancer treatment.