A new series of alkyl alpha-[5-(5-nitro-2-furyl)-1, 3, 4- thiadiazole-2-ylthio] and alpha-[5-(1-methyl-5-nitro-2-imidazolyl)-1, 3, 4-thiadiazole-2-ylthio]acetates (6a-e, 6f-j) were synthesized and evaluated against Mycobacterium tuberculosis as part of the TAACF (Tuberculosis Antimicrobial Acquisition and Coordinating Facility) TB screening program. Primary screening was conducted at the single concentration of 6.25 microg/mL against M. tuberculosis H(37)Rv in BACTEC 12B medium using a broth microdilution assay, the Microplate Alamar Blue Assay (MABA). The minimum inhibitory concentration (MIC) was determined for compounds demonstrating >90 % growth inhibition in the primary screening. Seven compounds were efficient antimycobacterial agents showing MIC values ranging from 0.78 to 6.25 microg/mL. Among nitrofuran derivatives, methyl (6a), ethyl (6b), and benzyl (6e) esters displayed a good antituberculosis activity (MIC=0.78-3.13 microg/mL) and the others were inactive. In the nitro imidazole series, methyl (6f), ethyl (6g), propyl (6h) and butyl (6i) esters showed significant activity against M. tuberculosis while benzyl (6j) ester was inactive. Also, active compounds were screened by serial dilution to assess toxicity to a VERO cell line. A varying degree of toxicity was observed in nitrofuran and nitroimidazole derivatives (IC(50) = 2.3 - >10 microg/mL).

Thiadiazole derivatives R 0300Synthesis, in vitro-Antimycobacterial Activity and Cytotoxicity of Some Alkyl α-(5-Aryl-1,3,4-thiadiazole-2-ylthio)acetates. -To establish the structure-activity relationships of 2-aryl-1,3,4-thiadiazoles, the synthesis of the title acetates (III) as antituberculosis agents is carried out. The majority of compounds display significant antituberculosis activity in the primary screening test. The active compounds are tested for cytotoxicity in VERO cells. Within the nitrofuran series, (IIIa) and (IIIb) show a high degree of toxicity, while in the nitroimidazole series, propyl and butyl esters (IIIc) and (IIId) exhibit a considerable low level cytotoxic effect. -(FOROUMADI*, A.; SOLTANI, F.; MOALLEMZADEH-HAGHIGHI, H.; SHAFIEE, A.; Arch. Pharm. (Weinheim, Ger.) 338 (2005) 2-3, 112-116; Dep. Med. Chem., Fac. Pharm., Kerman Univ. Med. Sci., Kerman, Iran; Eng.) -H. Hoennerscheid 34-180