Cytotoxicities and structure-activity relationships of natural and unnatural lamellarins toward cancer cell lines

Abstract

Twenty-two naturally occurring and three unnatural lamellarins 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-nanomolar (0.08 nm) to micromolar (>97.0 μm). About one-fourth (6/25) and one-half (11/25) of these lamellarins are more potent than the positive control, etoposide, against at least six different cell lines and three different cell types, respectively. In general, lamellarins D, X, ε, M, N, and dehydrolamellarin J are significantly more potent than the other lamellarins. The IC50 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 hydroxylation or methoxylation patterns for the first time, but also confirm prior findings and clarify some previous uncertainties. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA.