title: Synthesis, antimicrobial, anticancer evaluation and QSAR studies of 6-methyl-4-[1-(2-substituted-phenylamino-acetyl)-1H-indol-3-yl]-2-oxo/thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid ethyl esters.
abstract: A series of 6-methyl-4-[1-(2-substituted-phenylamino-acetyl)-1H-indol-3-yl]-2-oxo/thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid ethyl esters (1-16) were synthesized and evaluated in vitro for their antimicrobial and anticancer potential. 6-Methyl-4-{1-[2-(4-nitro-phenylamino)-acetyl]-1H-indol-3-yl}-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid ethyl ester (15, pMIC(ec) = 2.50 μM/mL) was found to be almost equipotent to the standard drug, norfloxacin (pMIC(ec) = 2.61 μM/mL) against Escherichia coli and emerged as most potent antimicrobial agent (pMIC(am) = 1.84 μM/mL). 4-{1-[2-(2-Chloro-4-nitro-phenylamino)-acetyl]-1H-indol-3-yl}-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid ethyl ester (4, IC(50) = 5 μg/mL) was more potent than the standard drug 5-fluorouracil (IC(50) = 6 μg/mL) against HCT-116 a colon cancer cell line, and emerged as the most potent anticancer agent. The QSAR studies demonstrated the importance of topological parameter, Balaban index (J) followed by lipophillic parameter, log P in describing the antimicrobial activity of the synthesized compounds.
authors.affiliation: Faculty of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak 124001, India.
authors.forename: Sandeep Kumar
authors.initials: SK
authors.lastname: Sharma
authors.forename: Pradeep
authors.initials: P
authors.lastname: Kumar
authors.forename: Balasubramanian
authors.initials: B
authors.lastname: Narasimhan
authors.forename: Kalavathy
authors.initials: K
authors.lastname: Ramasamy
authors.forename: Vasudevan
authors.initials: V
authors.lastname: Mani
authors.forename: Rakesh Kumar
authors.initials: RK
authors.lastname: Mishra
authors.forename: Abu Bakar Abdul
authors.initials: AB
authors.lastname: Majeed
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D007211:Indoles; D011743:Pyrimidines