Synthesis of diindolylmethane (DIM) bearing thiadiazole derivatives as a potent urease inhibitor

Muhammad Taha,Aftab Ahmad Khan,Naveed Ahmed,Mohamed Ibrahim,Fazal Rahim,El Hassane Anouar,Zainul Amiruddin Zakari,Syed Adnan Ali Shah

doi:10.1038/s41598-020-64729-3

Abstract

The current study describes synthesis of diindolylmethane (DIM) derivatives based-thiadiazole as a new class of urease inhibitors. Diindolylmethane is natural product alkaloid reported to use in medicinal chemistry extensively. Diindolylmethane-based-thiadiazole analogs (1–18) were synthesized and characterized by various spectroscopic techniques 1HNMR, 13C-NMR, EI-MS and evaluated for urease (jack bean urease) inhibitory potential. All compounds showed excellent to moderate inhibitory potential having IC50 value within the range of 0.50 ± 0.01 to 33.20 ± 1.20 µM compared with the standard thiourea (21.60 ± 0.70 µM). Compound 8 (IC50 = 0.50 ± 0.01 µM) was the most potent inhibitor amongst all derivatives. Structure-activity relationships have been established for all compounds. The key binding interactions of most active compounds with enzyme were confirmed through molecular docking studies.

Highlights

Urease (EC 3.5.1.5) belongs to the family of amidohydrolase enzymes having two nickel atoms in their core structure
Experimental results proved our previous hypothesis by obtaining good urease inhibitory potential of our synthesized molecules
We have found that inhibitory potential was greatly affected by the nature, position, and number of substituents

Summary

Introduction

Urease (EC 3.5.1.5) belongs to the family of amidohydrolase enzymes having two nickel atoms in their core structure. The most active compound among the series is analog 8 (IC50 = 0.50 ± 0.01 μM) having two-nitro groups at ortho and para position on phenyl ring.

Results

Conclusion