title: 5-((1-Aroyl-1H-indol-3-yl)methylene)-2-thioxodihydropyrimidine-4,6(1H,5H)-diones as potential anticancer agents with anti-inflammatory properties.
abstract: 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 μM), and OVCAR-3 (GI(50)=1.26 μM) ovarian cancer cell lines. The structurally related compound 3s had a GI(50) value of 1.77 μM against MDA-MB-435 cells. The N-naphthoyl analogue 3t had GI(50) values of 1.30 and 1.91 μM 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 μM 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.
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors: Narsimha Reddy
authors: NR
authors: Penthala
authors: Purushothama Rao
authors: PR
authors: Ponugoti
authors: Vinod
authors: V
authors: Kasam
authors: Peter A
authors: PA
authors: Crooks
mesh_terms: D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D011743:Pyrimidines; D013438:Sulfhydryl Compounds