UNLABELLED: 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.
UNLABELLED: 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.
Authors: Shivaputra A Patil; Jin Wang; Xiaochen S Li; Jianjun Chen; Terreia S Jones; Amira Hosni-Ahmed; Renukadevi Patil; William L Seibel; Wei Li; Duane D Miller Journal: Bioorg Med Chem Lett Date: 2012-04-24 Impact factor: 2.823
Authors: Yan Lu; Chien-Ming Li; Zhao Wang; Charles R Ross; Jianjun Chen; James T Dalton; Wei Li; Duane D Miller Journal: J Med Chem Date: 2009-03-26 Impact factor: 7.446