Hydrazone-Tethered 5-(Pyridin-4-yl)-4H-1,2,4-triazole-3-thiol Hybrids: Synthesis, Characterisation, in silico ADME Studies, and in vitro Antimycobacterial Evaluation and Cytotoxicity

Compounds containing arylpyrrole-, 1,2,4-triazole- and hydrazone structural frameworks have been widely studied and demonstrated to exhibit a wide range of pharmacological properties. Herein, an exploratory series of new 1,2,4-triazole derivatives designed by amalgamation of arylpyrrole and 1,2,4-triazole structural units via a hydrazone linkage is reported. The synthesised compounds were tested in vitro for their potential activity against Mycobacterium tuberculosis (MTB) H(37)Rv strain. The most promising compound 13 - the derivative without the benzene ring appended to the pyrrole unit displayed acceptable activity (MIC90=3.99 mu M) against MTB H(37)Rv, while other compounds from the series exhibited modest to weak antimycobacterial activity with MIC90 values in the range between 7.0 and > 125 mu M. Furthermore, in silico results, predicated using the SwissADME web tool, show that the prepared compounds display desirable ADME profile with parameters within acceptable range.

Automated summary

An exploratory series of new triazole derivatives were synthesized by combining arylpyrrole and triazole units via a hydrazone linkage. Compound 13 showed reasonable activity against Mycobacterium tuberculosis, but other compounds in the series displayed weak antimycobacterial activity.