Structure-activity relationship studies of arylthiazolidine amides as selective cytotoxic agents for melanoma.
New drugs are urgently needed for improved therapy for melanoma.


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.


CONCLUSIONS
The lead structure represents a novel class of compounds that can be further optimized for potential drug to treat advanced melanoma.
Li
Wei
W
Department of Pharmaceutical Sciences, College of Pharmacy, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA. wli@utmem.edu
Wang
Zhao
Z
Gududuru
Veeresa
V
Zbytek
Blazej
B
Slominski
Andrzej T
AT
Dalton
James T
JT
Miller
Duane D
DD
D000577:Amides / Q000737:chemistry* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001557:Benzenesulfonates / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D020128:Inhibitory Concentration 50; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D009336:Necrosis; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000494:pharmacology; D000077157:Sorafenib; D013329:Structure-Activity Relationship; D053778:Thiazolidines / Q000737:chemistry* / Q000494:pharmacology*
D000577:Amides; D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D053778:Thiazolidines; D009536:Niacinamide; D000077157:Sorafenib