Amides Derived From Sclareolide as Cytotoxic Agents

作者：Silva JG, de Miranda AS, Borgati TF, Lopes SMG, Hoenke S, Silva JO, Oliveira FFS, de Barros ALB, Sabino AP, Csuk R, Barbosa LCA · 发表于：Chemistry & biodiversity · 年份：2026 · DOI：10.1002/cbdv.71375 · 被引用次数：41 · 研究领域：Diterpenes、Antineoplastic Agents、Amides、Humans、Structure-Activity Relationship、Drug Screening Assays, Antitumor、Apoptosis、Cell Line, Tumor、Cell Proliferation、Cell Cycle、Molecular Structure

Natural products remain an invaluable source of inspiration for anticancer drug discovery. Herein, a series of 25 sclareolide (SC)-derived drimanamides was assessed for cytotoxicity against the A375, HT29, MCF-7, A2780, and HeLa tumor cell lines using the SRB assay. Structure-activity relationship analysis suggested that the introduction of aryl or triazolyl moieties was associated with increased potency relative to SC. Compounds 1 and 4 exhibited the most favorable cytotoxic profiles, with EC50 values of 9.2 µM (HT29) and 11.9 µM (MCF-7) and a selectivity index (SI) of 3.3 and 2.5, respectively. Annexin V/PI assays indicated that both 1 and 4 increased apoptotic populations in MCF-7 cells, while cell cycle analysis showed modest accumulation in the G1 and G2 phases for derivative 1 and an increased S-phase population for 4. These findings highlight the drimane nucleus as a useful scaffold for anticancer agent design, revealing drimanamides as a novel cytotoxic class and 1 and 4 as promising candidates for further optimization.