Synthesis, spectral studies and biological evaluation of a novel series of 2-substituted-5,6-diarylsubstituted imidazo(2,1-b)-1,3,4-thiadiazole derivatives as possible anti-tubercular agents

Abstract

A novel series of 18 analogs of 2-substituted-5,6-diarylsubstituted imidazo(2,1-b)-1,3,4-thiadiazole 6a-r have been synthesized by the reaction of 2-amino-5-substituted-1,3,4-thiadiazoles 5a-d and an appropriately substituted a-bromo-1,2-(p-substituted)diaryl-1-ethanones 4a-e. Structures of these compounds were established by physiochemical, elemental analysis and spectral data. All the title compounds were tested for their in-vitro anti-tubercular activity against Mycobacterium tuberculosis H 37 Rv using Alamar Blue susceptibility test and the activity expressed as the minimum inhibitory concentration (MIC) in lg/ml. Among synthesized compounds, compound 6h (MIC = 1.25 lg/ml) exhibited excellent anti-tubercular activity with respect to other synthesized compounds and reference drugs. Compounds 6c, 6f, and 6g have also displayed an encouraging anti-tubercular activity profile. Further, some title compounds were also assessed for their cytotoxic activity (IC 50 ) against in a mammalian Vero cell line using MTT assay. The results reveal that these compounds exhibit anti-tubercular activity at non-cytotoxic concentrations.

Recent Advances in the Research of Heterocyclic Compounds as Antitubercular Agents

“…As a result, thiophenyl-tethered dihydro-6H-quinolin-5-ones had better activity than aryl-tethered dihydro-6H-quinolin-5-ones. [42] Moreover, Kantevari and colleagues also synthesized another series of 18 new dihydroquinolines through CeCl 3 /7 H 2 O/NaI-catalyzed one-pot condensation of b-enaminones derived from the respective methyl ke-tones, 1,3-cyclohexanedione (or 5,5-dimethyl-1,3-cyclohexanedione), and ammonium acetate in 2-propanol. All the compounds showed better antimycobacterial activity than PZA, and, in particular, compound 75 (MIC = 3.1 mg mL À1 ) obtained through replacement of the bromine atom of compound 74 with chorine, was observed to be effective against M. tuberculosis H37Rv, more potent than EMB.…”

Ionic liquid-promoted one-pot synthesis of thiazole–imidazo[2,1-b][1,3,4]thiadiazole hybrids and their antitubercular activity

“…In view of this, the imidazoij2,1-b]ij1,3,4]thiadiazole (ITD) scaffold [2][3][4][5] is a promising heterocyclic moiety for developing efficient antitubercular leads. 6,7 The derivatives with a pharmacophoric substituent at position-5 of the ring exhibited significant inhibitory activity against the Mtb H37Rv strain. 8,9 For instance, Alegaon et al reported the synthesis and antitubercular evaluation of a series of 5-substituted ITD derivatives and the compound which contains a rhodanine acetic acid group (I, Fig.…”

The first catalyst and solvent-free synthesis of 2-arylimidazo[2,1-b][1,3,4]thiadiazoles: a comparative assessment of greenness

“…Fused heterocyclic structures over the last few decades have presented enormous opportunities in the elds of drug design and therapeutics. 1,2 The bicyclic core of imidazo[2,1-b][1,3,4]thiadiazoles 3 is one such scaffold widely manifested in an array of pharmacophoric activities 4 such as antihyperlipidemic, 5 antitubercular, 6 antitumor 7 and antimicrobial activities. 8 Some representative members of this class are displayed in Fig.…”