Synthesis, in vitro-antimycobacterial activity and cytotoxicity of some alkyl alpha-(5-aryl-1, 3, 4-thiadiazole-2-ylthio)acetates.
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).
Foroumadi
Alireza
A
Department of Medicinal Chemistry, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran. aforoumadi@yahoo.com
Soltani
Fatemeh
F
Moallemzadeh-Haghighi
Hamideh
H
Shafiee
Abbas
A
D000085:Acetates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002522:Chlorocebus aethiops; D008826:Microbial Sensitivity Tests; D009593:Nitroimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014709:Vero Cells
D000085:Acetates; D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents; D009593:Nitroimidazoles; D013830:Thiadiazoles