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A Novel Class Substituted Imidazo[2,1‐ b ][1,3,4]thiadiazole Derivatives: Synthesis, Characterization, In Vitro Biological Activity, and Potential Inhibitors Design Studies
Author(s) -
Er Mustafa,
Ahmadov Farid,
Karakurt Tuncay,
Direkel Şahin,
Tahtaci Hakan
Publication year - 2019
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201903886
Subject(s) - adme , chemistry , stereochemistry , benzonitrile , morpholine , docking (animal) , in vitro , medicinal chemistry , biochemistry , medicine , nursing
In this study, imidazo[2,1‐ b ][1,3,4]thiadiazole derivatives were designed and synthesized. All of the synthesized compounds were characterized by 1 H and 13 C nuclear magnetic resonance ( 1 H NMR and 13 C NMR), fourier‐transform infrared spectroscopy (FT‐IR), elemental analysis, mass spectrometry, and X‐ray diffraction. The synthesized compounds were tested for antileishmanial activity against two Leishmania species and antibacterial activity against nine bacterial species in the study. It was observed that 2‐(4‐Fluorobenzylthio)‐6‐(4‐fluorophenyl)imidazo[2,1‐ b ][1,3,4]thiadiazole ( 5 ) had the highest antileishmanial activity (MIC: 625 μg/mL). Also, 4‐(2‐(4‐fluorobenzylthio)imidazo[2,1‐ b ][1,3,4]thiadiazol‐6‐yl)benzonitrile ( 10 ), 2‐(4‐fluorobenzylthio)‐6‐(4‐phenylphenyl)imidazo[2,1‐ b ][1,3,4]thiadiazole ( 11 ), and 4‐(2‐(4‐methoxybenzyl)imidazo[2,1‐ b ][1,3,4]thiadiazol‐6‐yl)benzonitrile ( 25 ) were found to be effective at different studied concentrations. PyRx software, which uses a Lamarckian genetics algorithm, was utilized to find the affinity values of all compounds in molecular docking simulations. Pharmacokinetic properties and toxicities of the ligands were then researched using PROTOX (a webserver for the prediction of oral toxicities of small molecules) and FAF‐Drugs (free adsorption distribution, metabolism, excretion (ADME) tox filtering tool). The study showed that the ligands had acceptable toxicity and ADME properties for the inhibition of the 3JUS receptor.