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

Ogunyemi Olajide Oderinlo, Audrey Jordaan, Ronnett Seldon, Michelle Isaacs, Heinrich C. Hoppe, Digby F. Warner, Matshawandile Tukulula, Setshaba D. Khanye

2023ChemMedChem12 citationsDOIOpen Access PDF

Abstract

Abstract 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 (MIC 90 =3.99 μM) against MTB H 37 Rv, while other compounds from the series exhibited modest to weak antimycobacterial activity with MIC 90 values in the range between 7.0 and &gt;125 μM. Furthermore, in silico results, predicated using the SwissADME web tool, show that the prepared compounds display desirable ADME profile with parameters within acceptable range.

Topics & Concepts

AntimycobacterialADMEHydrazoneChemistryTriazoleIn silicoStereochemistryCombinatorial chemistry1,2,4-TriazoleMorpholinePharmacophorePyridazineIn vitroMycobacterium tuberculosisOrganic chemistryBiochemistryTuberculosisGeneMedicinePathologySynthesis and biological activityClick Chemistry and ApplicationsSynthesis and Biological Evaluation
Hydrazone‐Tethered 5‐(Pyridin‐4‐yl)‐4<i>H</i>‐1,2,4‐triazole‐3‐thiol Hybrids: Synthesis, Characterisation, <i>in silico</i> ADME Studies, and <i>in vitro</i> Antimycobacterial Evaluation and Cytotoxicity | Litcius