Author:
Khalili Ghomi Minoo,Noori Milad,Nazari Montazer Mohammad,Zomorodian Kamiar,Dastyafteh Navid,Yazdanpanah Somayeh,Sayahi Mohammad Hosein,Javanshir Shahrzad,Nouri Abbas,Asadi Mehdi,Badali Hamid,Larijani Bagher,Irajie Cambyz,Iraji Aida,Mahdavi Mohammad
Abstract
AbstractRegarding the important role of the urease enzyme as a virulence factor in urease-positive microorganisms in this study, new series of [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives were designed and synthesized. All compounds evaluated against urease enzyme exhibiting IC50 values of 0.87 ± 0.09 to 8.32 ± 1.21 µM as compared with thiourea as the positive control (IC50 = 22.54 ± 2.34 µM). The kinetic evaluations of 6a as the most potent derivative recorded a competitive type of inhibition. Molecular dynamic simulations of the 6a derivative were also conducted, showing that 6a occupied the active site with closed state. Antimicrobial activities of all derivatives were performed, and 6f (R = 3-Cl), 6g (R = 4-Cl), and 6h (R = 3,4-diCl) analogs demonstrated significant antifungal activities with MIC values of 1, 2, and 0.5 µg/mL compared with fluconazole with MIC = 2 µg/mL. Synthesized analogs also exhibited potent urease inhibitory activities against C. neoformans (IC50 = 83.7–118.7 µg/mL) and P. mirabilis (IC50 = 74.5–113.7 µg/mL), confirming their urease inhibitory potential. The results demonstrated that the designed scaffold could be considered a suitable pharmacophore to develop potent urease inhibitors.
Funder
Vice-Chancellor for Research, Shiraz University of Medical Sciences
Publisher
Springer Science and Business Media LLC
Cited by
3 articles.
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