5-Nitro-2,6-dioxohexahydro-4-pyrimidinecarboxamides: Synthesis, in vitro antimycobacterial activity, cytotoxicity, and isocitrate lyase inhibition studies

Journal of Enzyme Inhibition and Medicinal Chemistry

Volumn 25, Issue 6, 2010, Pages 765-772

  Sriram, Dharmarajan ^a   Yogeeswari, Perumal ^a   Senthilkumar, Palaniappan ^a   Naidu, Geetanjali ^a   Bhat, Pritesh ^a  

^a BIRLA INSTITUTE OF TECHNOLOGY AND SCIENCE   (India)

Author keywords

Antimycobacterial; Antitubercular; Isocitrate lyase; Orotic acid; Pyridinecarboxamides; Tuberculosis

Indexed keywords

1 CYCLOPROPYL 6 FLUORO 7 4 [(5 NITRO 2,6 DIOXOHEXAHYDRO 4 PYRIMIDINYL)CARBONYL]PIPERAZINO 4 OXO 1,4 DIHYDRO 3 QUINOLINE CARBOXYLIC ACID; 1 CYCLOPROPYL 6 FLUORO 8 METHOXY 7 (3 METHYL) 4 [(5 NITRO 2,6 DIOXOHEXAHYDRO 4 PYRIMIDINYL)CARBONYL]PIPERAZINO 4 OXO 1,4 DIHYDRO 3 QUINOLINE CARBOXYLIC ACID; 1 ETHYL 6 FLUORO 7 4 [(5 NITRO 2,6 DIOXOHEXAHYDRO 4 PYRIMIDINYL)CARBONYL]PIPERAZINO 4 OXO 1,4 DIHYDRO 3 QUINOLINE CARBOXYLIC ACID; 3 NITROPROPIONIC ACID; 5 NITRO 2,6 DIOXO N PHENYLHEXAHYDRO 4 PYRIMIDINE CARBOXAMIDE; 5 NITRO 2,6 DIOXOHEXAHYDRO 4 PYRIMIDINE CARBOXAMIDE DERIVATIVE; 5 NITRO 6 [(4 PHENYLPIPERAZINO)CARBONYL]DIHYDRO 2,4(1H,3H) PYRIMIDINEDIONE; 5 NITRO 6 [4 [3 (TRIFLUOROMETHYL)PHENYL]PIPERAZINOCARBONYL]DIHYDRO 2,4(1H,3H) PYRIMIDINEDIONE; 6 [4 (4 CHLOROPHENYL)PIPERAZINO]CARBONYL 5 NITRODIHYDRO 2,4(1H,3H) PYRIMIDINEDIONE; 6 [4 (4 FLUOROPHENYL)PIPERAZINO]CARBONYL 5 NITRODIHYDRO 2,4(1H,3H) PYRIMIDINEDIONE; 6 [4 (4 METHOXYPHENYL)PIPERAZINO]CARBONYL 5 NITRODIHYDRO 2,4(1H,3H) PYRIMIDINEDIONE; 7 (3,5 DIMETHYL) 4 [(5 NITRO 2,6 DIOXOHEXAHYDRO 4 PYRIMIDINYL)CARBONYL]PIPERAZINO 1 ETHYL 6,8 DIFLUORO 4 OXO 1,4 DIHYDRO 3 QUINOLINE CARBOXYLIC ACID; ANTIMYCOBACTERIAL AGENT; CIPROFLOXACIN; ISOCITRATE LYASE; ISONIAZID; N(2,4 DINITROPHENYL) 5 NITRO 2,6 DIOXOHEXAHYDRO 4 PYRIMIDINE CARBOXAMIDE; N(4 BROMOPHENYL) 5 NITRO 2,6 DIOXOHEXAHYDRO 4 PYRIMIDINE CARBOXAMIDE; N(4 CHLOROPHENYL) 5 NITRO 2,6 DIOXOHEXAHYDRO 4 PYRIMIDINE CARBOXAMIDE; N(5 BROMO 2 PYRIDINYL) 5 NITRO 2,6 DIOXOHEXAHYDRO 4 PYRIMIDINE CARBOXAMIDE; RIFAMPICIN; UNCLASSIFIED DRUG;

ANIMAL CELL; ANTIMICROBIAL ACTIVITY; ARTICLE; CELL VIABILITY; CONTROLLED STUDY; CYTOTOXICITY; DRUG SYNTHESIS; ENZYME INHIBITION; IN VITRO STUDY; MINIMUM INHIBITORY CONCENTRATION; MYCOBACTERIUM SMEGMATIS; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; PRIORITY JOURNAL; VERO CELL;

ANIMALS; ANTI-BACTERIAL AGENTS; ANTITUBERCULAR AGENTS; BACTERIAL PROTEINS; CERCOPITHECUS AETHIOPS; COMPUTER SIMULATION; DRUG EVALUATION, PRECLINICAL; DRUG RESISTANCE, MULTIPLE, BACTERIAL; ENZYME INHIBITORS; INHIBITORY CONCENTRATION 50; ISOCITRATE LYASE; LIGANDS; MICROBIAL SENSITIVITY TESTS; MOLECULAR STRUCTURE; MYCOBACTERIUM; MYCOBACTERIUM SMEGMATIS; MYCOBACTERIUM TUBERCULOSIS; PIPERAZINES; PROTEIN BINDING; PYRIMIDINES; QUINOLINES; TUBERCULOSIS; VERO CELLS;

MYCOBACTERIUM SMEGMATIS; MYCOBACTERIUM TUBERCULOSIS;

EID: 78149421997     PISSN: 14756366     EISSN: 14756374     Source Type: Journal    
DOI: 10.3109/14756360903425221     Document Type: Article

References (16)

1. World Health Organization. Global tuberculosis control: surveillance, planning, financing: WHO report 2008. Geneva: WHO, 2008.
2. Sriram D, Yogeeswari P, Dinakaran M, Thirumurugan R. Antimycobacterial activity of novel 1-(5-cyclobutyl-1,3-oxazol-2-yl)-3-(sub)phenyl/ pyridylthiourea endowed with high activity toward multi-drug resistant tuberculosis. J Antimicrob Chemother 2007;59:1194-6.
3. Sriram D, Senthilkumar P, Dinakaran M, Yogeeswari P, China A, Nagaraja V. Antimycobacterial activities of novel 1-(cyclopropyl/ tert-butyl/4- fluorophenyl)-1,4-dihydro-6-nitro-4-oxo-7-(substituted secondary amino)-1,8-naphthyridine-3-carboxylic acid. J Med Chem 2007;50:6232-9.
4. Kumar RR, Perumal S, Senthilkumar P, Yogeeswari P, Sriram D. Discovery of antimycobacterial spiro-piperidin-4-ones: an atom economic, stereoselective synthesis, and biological intervention. J Med Chem 2008; 51:5731-5.
5. Dinakaran M, Senthilkumar P, Yogeeswari P, China A, Nagaraja V, Sriram D. Antimycobacterial and phototoxic evaluation of novel 6-fluoro/ nitro-4-oxo-7-(sub)-4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylic acid. Int J Antimicrob Agents 2008;31:337-44.
6. Dinakaran M, Senthilkumar P, Yogeeswari P, China A, Nagaraja V, Sriram D. Novel ofloxacin derivatives: synthesis, antimycobacterial and toxicological evaluation. Bioorg Med Chem 2008;16:3408-18.
7. Sriram D, Yogeeswari P, Thirumurugan R, Pavana RK. Discovery of newer antitubercular oxazolyl thiosemicarbazones. J Med Chem 2006; 49:3448-50.
8. Dinakaran M, Senthilkumar P, Yogeeswari P, China A, Nagaraja V, Sriram D. Synthesis, antimycobacterial activities and phototoxic evaluation of 5H-thiazolo[3,2-a]quinoline-4-carboxylic acid derivatives. Med Chem 2008;4:482-91.
9. Kumar RR, Perumal S, Senthilkumar P, Yogeeswari P, Sriram D. An atom efficient, solvent-free, green synthesis and antimycobacterial evaluation of 2-amino-6-methyl-4-aryl-8-[(E)-arylmethylidene]-5,6,7,8-tetrahydro- 4H-pyrano[3,2-c]pyridine-3-carbonitriles. Bioorg Med Chem Lett 2007;17:6459-62.
10. National Committee for Clinical Laboratory Standards. Antimycobacterial susceptibility testing for Mycobacterium tuberculosis. Proposed standard M24-T. Villanova, PA: National Committee for Clinical Laboratory Standards. 1995.
11. Xie Z, Siddiqi N, Rubin ER. Differential antibiotic susceptibilities of starved Mycobacterium tuberculosis isolates. Anitimicrob Agents Chemother 2005;49:4778-80.
12. Bai B, Xie JP, Yan JF, Wang H, Hu C. A high throughput screening approach to identify isocitrate lyase inhibitors from traditional Chinese medicine sources. Drug Dev Res 2006;67:818-23.
13. Gundersen LL, Meyer NJ, Spilsberg B. Synthesis and antimycobacterial activity of 6-arylpurines: the requirements for the N-9 substituent in active antimycobacterial purines. J Med Chem 2002;45:1383-6.
14. Jones G, Willett P, Glen RC, Leach AR, Taylor R. Development and validation of a genetic algorithm for flexible docking. J Mol Biol 1997; 267:727-48.
15. Mc Kinney JD. Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase. Nature 2000;406:735-8.
16. Bentrup KHZ, Miczak A, Swenson DL, Russell DG. Characterization of activity and expression of isocitrate lyase in Mycobacterium avium and Mycobacterium tuberculosis. J Bacteriol 1999;181:7161-7.