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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:23

Article

Penthala, Narsimha Reddy¹  Ponugoti, Purushothama Rao¹  Kasam, Vinod¹  Crooks, Peter A.¹ 

[1] Univ Arkansas Med Sci, Coll Pharm, Dept Pharmaceut Sci, Little Rock, AR 72205 USA

关键词: N-Benzoyl indole-3-carboxaldehydes;    N-Naphthoylindole-3-carboxaldehydes;    Thiobarbituric acid;    In vitro cytotoxicity;    Anti-inflammatory agents;   

DOI  :  10.1016/j.bmcl.2012.12.053

来源: Elsevier

【 摘 要 】

A series of novel 5-((1-aroyl-1H-indol-3-yl)methylene)-2-thioxodihydropyrimidine-4,6(1H,5H)-diones (3a-z) have been evaluated for in vitro cytotoxicity against a panel of 60 human tumor cell lines. Compound 3k exhibited the most potent growth inhibition against melanoma MDA-MB-435 cells (GI(50) = 850 nM), against leukemia SR cancer cells (GI(50) = 1.45 mu M), and OVCAR-3 (GI(50) = 1.26 mu M) ovarian cancer cell lines. The structurally related compound 3s had a GI(50) value of 1.77 mu M against MDA-MB-435 cells. The N-naphthoyl analogue 3t had GI(50) values of 1.30 and 1.91 mu M against HOP-92 non-small cell lung cancer and MDA-MB-435 melanoma cell lines, respectively. The related analogue 3w had GI(50) values of 1.09 mu M against HOP-92 non-small cell lung cancer cell lines. Interestingly, docking of the two active molecules 3k and 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 3k, 3t, 3s, and 3w constitute a new class of anticancer/anti-inflammatory agents that may have unique potential for cancer therapy. (C) 2013 Elsevier Ltd. All rights reserved.

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