5-((1-Aroyl-1H-indol-3-yl)methylene)-2-thioxodihydropyrimidine-4,6(1H,5H)-diones as potential anticancer agents with anti-inflammatory properties

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• 作者：Narsimha Reddy Penthala ; Purushothama Rao Ponugoti ; Vinod Kasam ; Peter A. Crooks ; ^{pacrooks@uams.edu}
• 关键词：N-Benzoyl indole-3-carboxaldehydes ; N-Naphthoylindole-3-carboxaldehydes ; Thiobarbituric acid ; In vitro cytotoxicity ; Anti-inflammatory agents
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2013
• 出版时间：1 March, 2013
• 年：2013
• 卷：23
• 期：5
• 页码：1442-1446
• 全文大小：507 K

文摘

A series of novel 5-((1-aroyl-1H-indol-3-yl)methylene)-2-thioxodihydropyrimidine-4,6(1H,5H)-diones (ass=""boldFont"">3a-ass=""boldFont"">z) have been evaluated for in vitro cytotoxicity against a panel of 60 human tumor cell lines. Compound ass=""boldFont"">3k exhibited the most potent growth inhibition against melanoma MDA-MB-435 cells (GI₅₀ = 850 nM), against leukemia SR cancer cells (GI₅₀ = 1.45 ¦ÌM), and OVCAR-3 (GI₅₀ = 1.26 ¦ÌM) ovarian cancer cell lines. The structurally related compound ass=""boldFont"">3s had a GI₅₀ value of 1.77 ¦ÌM against MDA-MB-435 cells. The N-naphthoyl analogue ass=""boldFont"">3t had GI₅₀ values of 1.30 and 1.91 ¦ÌM against HOP-92 non-small cell lung cancer and MDA-MB-435 melanoma cell lines, respectively. The related analogue ass=""boldFont"">3w had GI₅₀ values of 1.09 ¦ÌM against HOP-92 non-small cell lung cancer cell lines. Interestingly, docking of the two active molecules ass=""boldFont"">3k and ass=""boldFont"">3w into the active site of COX-2 indicates that these compounds are COX-2 ligands with strong hydrophobic and hydrogen bonding interactions. Thus, compounds ass=""boldFont"">3k, ass=""boldFont"">3t, ass=""boldFont"">3s, and ass=""boldFont"">3w constitute a new class of anticancer/anti-inflammatory agents that may have unique potential for cancer therapy.