Synthesis and Antituberculosis Activity of Cycloalkylidenehydrazide and 4-Aza-1-thiaspiro [4.5] decan-3-one Derivatives of Imidazo [2][1-b]thiazole

Abstract

New N2-cycloalkylidene-(6-phenyl/4-chlorophenylimidazo[2,1-b]thiazol-3-yl) acetic acid hydrazides (2a-h and 3a-b) were synthesized by reacting (6-phenyl/4-chlorophenylimidazo[2,1-b]thiazol-3-yl)acetic acid hydrazides with cyclohexanones or cyclopentanone. Furthermore, 2a-h were refluxed with thioglycolic or thiolactic acid to give 4-[[(6-phenyl/4-chlorophenylimidazo[2,1-b]thiazol-3-yl) acetyl]amino]-4-aza-1-thiaspiro[4.5]decan-3-ones (4a-h and 5a-h). The structures of the title compounds were established by spectral data (IR, 1H-NMR, 13C-NMR and EIMS (Electron Impact Mass Spectrometry)) and elemental analysis. The synthesized compounds were evaluated for antituberculosis activity against Mycobacterium tuberculosis H37Rv (ATCC 27294). The compounds exhibited varying degrees of inhibition in the in vitro primary screening that was conducted at a concentration of 6.25 micrograms/ml against M. tuberculosis H37Rv (ATCC 27294) in Bactec 12B medium using the Bactec 460 radiometric system or a broth microdilution assay, the Microplate Alamar Blue Assay (MABA). Compounds 2f, 2h, 3b, 4a, 4c, 4d, 5a-e and 5h demonstrating at 1-east 90% inhibition in the primary screen were re-tested at lower concentrations against M. tuberculosis H37Rv (ATCC 27294) to determine the actual minimum inhibitory concentration (MIC) using MABA. The most active compounds were found to be 4d and 5c. The structure-activity relationships of the derivatives were investigated.

An experimental and mechanism study on the regioselective click reaction toward the synthesis of thiazolidinone-triazole

“…Recently, several computational studies were presented on the mechanism of click reaction in the presence of different catalyst including Ru, Cu, Mg which results different regioselectivity [19,27,28,29,30,31,32,33]. On the other hand, thiazolidinone derivatives have been the subject to considerable studies, because of important biological applications such as antibacterial [34,35,36,37,38], antiviral [39,40,41], antifungal [42,43,44] and antituberculosis properties [35,45,46].…”

Synthesis of a New Class of Tris‐ and Bis(1,3,4‐thiadiazol‐2‐amine) Methyl and Ethyl Tris‐ and Bis‐2‐(2‐(2‐benzoyl hydrazinyl)‐4‐oxothiazolidine) Acetate Derivatives

“…It has also been reported in literature that certain compounds bearing 1,3,4-oxadiazole/thiadiazole and 1,2,4-triazole nucleus possess signi�cant anti-in�ammatory activity [5][6][7]. 4-iazolidinone derivatives are also known to possess antibacterial [8][9][10][11], antifungal [12][13][14], antiviral [15][16][17][18], and antituberculosis [19][20][21] properties. 4-iazolidinones have been reported as novel inhibitors of the bacterial enzyme [22].…”

Preparation and evaluation of antibacterial activity of some new 1,2,4‐triazole derivatives

“…Studies on 1,2,4-triazole compounds have a wide range in the area of pharmacology [7][8][9][10][11][12][13][14]. 4-Thiazolidinones are known to possess antibacterial [15][16][17][18][19][20], antifungal [21], antiviral [22,23], and antituberculosis [24] properties ( Fig. 1).…”