Synthesis, in vitro‐Antimycobacterial Activity and Cytotoxicity of Some Alkyl α‐(5‐aryl‐1, 3, 4‐thiadiazole‐2‐ylthio)acetates

Abstract

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).

Syntheses and antibacterial studies of some 2-[5-(Aryl)-[1,3,4]oxadiazole-2-ylsulfanyl] alkanoic Acids

“…Further, [5-(aryl)-1,3,4-thiadiazole-2-ylthio]acetates and propionates have been found to possess antimycobacterial activity [11][12][13][14]. These reports including our earlier work [15,16] prompted us to undertake the synthesis of some 2-[5-(aryl)-1,3,4-oxadiazole-2-ylsulfanyl]alkanoic acids.…”

Synthesis, evaluation and in silico molecular modeling of pyrroyl-1,3,4-thiadiazole inhibitors of InhA

“…The INH-NADH adduct functions as a potent inhibitor of InhA and other InhA inhibitors like diazaborines, triclosan, pyrazole derivatives and indole-5-amides have been reported earlier [11][12][13][14][15]. The 1,3,thiadiazoles and their analogs are the well known antimicrobial agents due to the presence of toxophoric AN@CAS moiety, which exhibits a broad spectrum of biological activities [16][17][18][19][20][21][22][23]. Based on our previous reports on pyrrole derivatives [24][25][26][27], we find it necessary to further develop pyrrolyl aryloxy thiadiazole derivatives as the effective anti-tubercular (anti-TB) agents.…”

Synthesis of novel spiro(indolone‐3,2′‐[1,3,4]thiadiazol)‐2‐ones and evaluation of their antidepressant and anticonvulsant activities

“…Antidepressants and anticonvulsants are among the most widely utilized drugs for the treatment of central nervous system (CNS) disorders [1–4]. The 1,3,4‐thiadiazole core is found to be the active part of several biologically active compounds, including antibacterial [5–8], antifungal [7, 8], antitubercular [9–11], analgesic [12], anti‐inflammatory [7, 8, 13], antidepressant [14], and leishmanicidal agents [15]. Isatin is an endogenous compound isolated, and reported to possess a wide range of central nervous system activities [16–18].…”