Antituberculosis agents X. Synthesis and evaluation of in vitro antituberculosis activity of 2-(5-nitro-2-furyl)- and 2-(1-methyl-5-nitro-1H-imidazol-2-yl)-1,3,4-thiadiazole derivatives.

摘要

Two series of 2-(5-nitro-2-furyl)- and 2-(1-methyl-5-nitro-1H-imidazol-2-yl)-5-propyl, allyl and propargyl)thio-1,3,4-thiadiazoles (6a-f) and 2-(5-nitro-2-furyl)- and 2-(1-methyl-5-nitro-1H-imidazol-2-yl)-5-(nitrobenzyl)thio-1,3,4-thiadiazol e derivatives (8a-f) have been synthesized and evaluated against Mycobacterium tuberculosis, as part of the TAACF TB screening program under direction of the US National Institute of Health, the NIAID division. Primary screening was conducted at a single concentration, 6.25 microg mL(-1), against M. tuberculosis H37Rv in BACTEC 12B medium, using the Microplate Alamar Blue Assay (MABA). The minimum inhibitory concentration (MIC) was determined for the compounds that demonstrated > or = 90% growth inhibition in the primary screening. A varying degree of antituberculosis activity (from 0-97% of growth inhibition) was observed with the alkylthio series (6a-f), and the nitroimidazole derivative with a propylthio group (6b) and the nitrofuran derivative with a propargylthio group (6e), were the most active compounds (MIC=3.13 and 1.56 microg mL(-1), respectively). Among the nitrobenzylthio derivatives (8a-f), all the ortho, meta and para nitrobenzyl isomers in the nitrofuran series exhibited good antituberculosis activity (MIC=3.13 microg mL(-1)), while the corresponding nitroimidazole analogues were completely inactive (Inhibition=0%).