Cytotoxicities and Structure-Activity Relationships of Natural and Unnatural Lamellarins toward Cancer Cell Lines

摘要

Twenty-two naturally occurring and three unnatural larnellarins were synthesized and evaluated for their cytotoxicities against cancer cells. Across eleven cancer cell lines derived from six different cancer types, the IC_(50) values of these compounds ranged from sub-nanOmoiar (0.08 nM) to micromolar (>97.0μm). About one-fourth (6/25) and one-half (11/25) of these larnellarins are more potent than the positive control, etoposide, against at least six different cell lines and three different cell types, respectively. In general, larnellarins D, X, ε, M, N, and dehydrolamellarin J are significantly more potent than the other larnellarins. The IC_(50) values were used to perform structure-activity relationship (SAR) studies by comparing the cytotoxic activities of several pairs of lamellarin structures that differ in selected substitution patterns. Our results not only reveal the importance of specific hydroxyl-ation or methoxylation patterns for the first time, but also confirm prior findings and clarify some previous uncertainties.