Structure-activity relationship studies of arylthiazolidine amides as selective cytotoxic agents for melanoma

Abstract

New drugs are urgently needed for improved therapy for melanoma.

Materials and methods: Ninety-one novel compounds were evaluated in two melanoma and one normal skin cell lines to identify potential lead compounds with high potency and selectivity. Mechanisms of action for the best compound were also investigated.

Results: Three potent lead structures (serine amino alcohols, serine amides and thiazolidines) were identified, with thiazolidines having both excellent potency and high selectivity when compared with sorafenib, a drug used extensively in clinical trials for melanoma. Analyzing the effect of the lead compound showed that it induced DNA degradation consistent with necrotic cell death.

Conclusion: The lead structure represents a novel class of compounds that can be further optimized for potential drug to treat advanced melanoma.