Antituberculosis agents x. synthesis and evaluation ofIn Vitro antituberculosis activity of 2-(5-nitro-2-furyl)- and 2-(1-methyl-5-nitro-1H-imidazol-2-yl)-1,3,4-thiadiazole derivatives

Abstract

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-thiadiazole 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%).

Structural and vibrational studies on 1-(5-methyl-[1,3,4] thiadiazol-2-yl)-pyrolidin-2-ol

“…The S 16 43.93kJ/mol to π*N 1 -C 5 . The maximum hyperconjugativeE (2) energy of heteroatoms during the intra-molecular interaction leads the molecule towards medicinal and biological applications.…”

“…The synthesis of novel thiadiazole derivatives and investigation of their chemical and biological behavior have gained more importance in recent decades. During recent years, an intense investigation of different classes of thiadiazole compounds in many of which are known to possess vast biological properties such as antimicrobial [1], antituberculosis [2,3], anti-inflammatory [4,5], analgesic [6], anticonvulsant [7], antihypertensive [8], antioxidant [9] anticancer [10,11], antifungal [12,13], antiviral [14], antidepressant [15], antibacterial [16][17][18] and antitumour [19]. Thiadiazole become very important compound in medicine, agriculture, and many fields of technology.…”

Synthetic Nitroimidazoles: Biological Activities and Mutagenicity Relationships

“…Tuberculosis inhibition activity and cytotoxicity results of these derivatives were not better or at least similar to the control drugs INH and rifampicin (RMP). 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 (19a-f) and 2-(5-nitro-2-furyl)-and 2-(1-methyl-5-nitro-1H-imidazol-2-yl)-5-(nitrobenzyl)thio-1,3,4-thiadiazole derivatives (20a-f) were synthesized and evaluated against M. tb ( Figure 3) [71]. Among the nitrobenzylthio derivatives (20a-f), all the ortho, meta and para nitrobenzyl isomers in the nitrofuran series exhibited good antituberculosis activity, while the corresponding nitroimidazole analogues were completely inactive (Inhibition=0%).…”

Synthesis of α‐[5‐(5‐amino‐1,3,4‐thiadiazol‐2‐yl)‐2‐imidazolylthio]acetic acids

“…Recently the synthesis of some alkyl -(5-aryl-1,3,4 -thiadiazol-2-ylthio)acetates and 2-(5-nitro-2-furyl)-and 2-(1-methyl-5-nitro-1H-imidazol-2-yl)-1,3,4-thiadiazole derivatives as potential antituberculosis agents has been reported [3,4]. The 1,3,4-thiadiazole ring system have incorporated in many substances with antibacterial, amoebicide, parasiticide and antifungal activity [5,6].…”