Design, Synthesis, Characterization and Computational Studies of Mannich Bases Oxadiazole Derivatives as New Class of Jack Bean Urease Inhibitors.

Autor: Mutahir S; School of Chemistry and Chemical Engineering, Linyi University, Linyi, 276000, China., Khan MA; School of Chemistry and Chemical Engineering, Linyi University, Linyi, 276000, China., Almehizia AA; Drug Exploration and Development Chair (DEDC), Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia., Abouzied AS; Department of Pharmaceutical Chemistry, College of Pharmacy, University of Hail, Hail, 81442, Saudi Arabia.; Department of Pharmaceutical Chemistry, National Organization for Drug Control and Research (NODCAR), Giza, 12553, Egypt., Khalifa NE; Department of pharmaceutics, College of Pharmacy, University of Hail, Hail, 81442, Saudi Arabia.; Department of pharmaceutics, Faculty of Pharmacy, University of Khartoum, Khartoum, 11115, Sudan., Naglah AM; Drug Exploration and Development Chair (DEDC), Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia., Deng H; School of Pharmacy, Nanjing University of Traditional Chinese Medicine, Nanjing, 210094, China., Refat MS; Department of Chemistry, College of Science, Taif University, P.O. Box 11099, Taif, 21944, Saudi Arabia., Khojali WMA; Department of Pharmaceutical Chemistry, College of Pharmacy, University of Hail, Hail, 81442, Saudi Arabia.; Department of pharmaceutical chemistry, faculty of pharmacy, Omdurman Islamic University, Omdurman, 14415, Sudan., Huwaimel B; Department of Pharmaceutical Chemistry, College of Pharmacy, University of Hail, Hail, 81442, Saudi Arabia.; Medical and Diagnostic Research Center, University of Hail, Hail, 81442, Saudi Arabia.
Jazyk: angličtina
Zdroj: Chemistry & biodiversity [Chem Biodivers] 2023 Aug; Vol. 20 (8), pp. e202300241. Date of Electronic Publication: 2023 Jul 26.
DOI: 10.1002/cbdv.202300241
Abstrakt: Mannich bases consisting of 1,3,4-oxadiazole-2-thione (3 a-3 l) bearing various substituents were synthesized and found potent jack bean urease inhibitors. The prepared compounds showed significantly good inhibitory activities with IC 50 values from 9.45±0.05 to 267.42±0.23 μM. The compound 3 k containing 4-chlorophenyl (-R) and 4-hydroxyphenyl (-R') was most active with IC 50 9.45±0.05 μM followed by 3 e (IC 50 22.52±0.15 μM) in which -R was phenyl and -R' was isopropyl group. However, when both -R and -R' were either 4-chlorophenyl groups (3 l) or only -R' was 4-nitrophenyl (3 i), both compounds were found inactive. The detailed binding affinities of the produced compounds with protein were explored through molecular docking and data-supported in-vitro enzyme inhibition profiles. Drug likeness was confirmed by in silico ADME investigations and molecular orbital analysis (HOMO-LUMO) and electrostatic potential maps were got from DFT calculations. ESP maps exposed that there are two potential binding sites with the most positive and most negative parts.
(© 2023 Wiley-VHCA AG, Zurich, Switzerland.)
Databáze: MEDLINE
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