Heterocyclic benzazole derivatives with antimycobacterial in vitro activity

Bioorganic and Medicinal Chemistry Letters

Volumn 12, Issue 22, 2002, Pages 3275-3278

  Kočí, Jan ^a   Klimešová, Věra ^a   Waisser, Karel ^a   Kaustová, Jarmila ^b   Dahse, Hans Martin ^c   Möllmann, Ute ^c  

^a Charles University in Prague Faculty of Pharmacy   (Czech Republic)

^b Regional Institute of Hygiene   (Czech Republic)

^c HANS KNÖLL INSTITUTE   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

2 BENZYLSULFANYL DERIVATIVE; BENZENE DERIVATIVE; BENZOTHIAZOLE; BENZOXAZOLE DERIVATIVE; HETEROCYCLIC COMPOUND; NITRO DERIVATIVE; THIOAMIDE; UNCLASSIFIED DRUG; ANTIINFECTIVE AGENT;

ANTIBACTERIAL ACTIVITY; ARTICLE; ASSAY; BACTERIAL STRAIN; CONTROLLED STUDY; CYTOTOXICITY; DRUG STRUCTURE; DRUG SYNTHESIS; IN VITRO STUDY; MINIMUM INHIBITORY CONCENTRATION; MYCOBACTERIUM AVIUM; MYCOBACTERIUM KANSASII; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; TUBERCULOSIS; DRUG EFFECT; HELA CELL; HUMAN; MICROBIOLOGICAL EXAMINATION; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

CORYNEBACTERINEAE; MYCOBACTERIUM; MYCOBACTERIUM TUBERCULOSIS;

ANTI-BACTERIAL AGENTS; BENZOXAZOLES; HELA CELLS; HUMANS; MICROBIAL SENSITIVITY TESTS; MYCOBACTERIUM AVIUM; MYCOBACTERIUM KANSASII; MYCOBACTERIUM TUBERCULOSIS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0037131751     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(02)00697-2     Document Type: Article

References (14)

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10. General procedure for the preparation of compounds 4a-h, 5a-h. Benzazole-2-thiol ( 1, 2 ) (5 mmol) in dry DMF (8 mL) was added to a solution of sodium (5 mmol) in dry ethanol (2.5 mL). After 10 min of stirring at ambient temperature, benzyl halide ( 3 ) (5mmol) was added in 2-3 portions, and the resultant suspension was stirred for 2-6 h. The reaction mixture was then poured into an ice bath and left at it overnight. The solid was filtered off, washed with cold water (2×30 mL) and air-dried. The crude product was purified by preparative TLC using acetone-light petroleum (1:2, 1:3, 1:4, 1:5, 1:6), followed by crystallization from ethanol (95%)
11. General procedure for the preparation of compounds 4i, 4j, 5i, 5j. Dry hydrogen sulfide was passed through a solution of cyano compounds 4g, 4h, 5g, 5h (2 mmol) dissolved in a mixture of dry pyridine (7 mL) and triethylamine (0.7 mL). The reaction mixture was maintained at ambient temperature for 3 h and then heated at 45 °C for additional h. After cooling, the mixture was poured onto crushed ice with intensive stirring, the precipitated product was filtered off, washed with cold water (2×35 mL) and air-dried. Performed preparative TLC chromatography using acetone-light petroleum (1:1, 1:2) and crystallization from ethanol (95%) yielded products 4i, 4j, 5i, 5j as yellow crystals in 35-66% yield.
12. All strains were obtained from the Czech National Collection of Type Cultures (CNCTC), with the exception of M. kansasii 6509/96, which was a clinical isolate. The antimycobacterial activities of the compounds were determined in the Šula semisynthetic medium (SEVAC, Prague). The compounds were added to the medium in dimethylsulfoxide solutions. The following concentrations were used: 500, 250, 125, 62, 32, 16, 8, 4, and 2 (μmol/L). MICs were determined after incubation at 37 °C for 7, 14, and 21 days. MIC was the lowest concentration of the substance, at which the inhibition of the growth of mycobacteria occurred.
13. 3: C 56.93, H 3.82, N 8.85, S 30.39. Found: C 56.76, H 3.95, N 8.65, S 30.27.
14. Dahse H.-M., Schlegel B., Gräfe U. Differentiation between inducers of apoptosis and nonspecific cytotoxic drugs by means of cell analyzer and immunoassay. Pharmazie. 56:2001;489.