Synthesis and urease inhibitory potential of benzophenone sulfonamide hybrid in vitro and in silico

Arshia; Farida Begum; Noor Barak Almandil; Muhammad Arif Lodhi; Khalid Mohammed Khan; Abdul Hameed; Shahnaz Perveen

doi:10.1016/j.bmc.2019.01.043

Synthesis and urease inhibitory potential of benzophenone sulfonamide hybrid in vitro and in silico

Bioorg Med Chem. 2019 Mar 15;27(6):1009-1022. doi: 10.1016/j.bmc.2019.01.043. Epub 2019 Feb 2.

Authors

Arshia¹, Farida Begum², Noor Barak Almandil³, Muhammad Arif Lodhi², Khalid Mohammed Khan⁴, Abdul Hameed¹, Shahnaz Perveen⁵

Affiliations

¹ H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
² Abdul Wali Khan University Mardan, Khyber Pakhtunkhwa 23200, Pakistan.
³ Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 31441, Dammam, Saudi Arabia.
⁴ H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan; Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 31441, Dammam, Saudi Arabia. Electronic address: khalid.khan@iccs.edu.
⁵ PCSIR Laboratories Complex, Shahrah-e-Dr. Salimuzzaman Siddiqui, Karachi 75280, Pakistan.

PMID: 30738655
DOI: 10.1016/j.bmc.2019.01.043

Abstract

This study deals with the synthesis of benzophenone sulfonamides hybrids (1-31) and screening against urease enzyme in vitro. Studies showed that several synthetic compounds were found to have good urease enzyme inhibitory activity. Compounds 1 (N'-((4'-hydroxyphenyl)(phenyl)methylene)-4''-nitrobenzenesulfonohydrazide), 2 (N'-((4'-hydroxyphenyl)(phenyl)methylene)-3''-nitrobenzenesulfonohydrazide), 3 (N'-((4'-hydroxyphenyl)(phenyl)methylene)-4''-methoxybenzenesulfonohydrazide), 4 (3'',5''-dichloro-2''-hydroxy-N'-((4'-hydroxyphenyl)(phenyl)methylene)benzenesulfonohydrazide), 6 (2'',4''-dichloro-N'-((4'-hydroxyphenyl)(phenyl)methylene)benzenesulfonohydrazide), 8 (5-(dimethylamino)-N'-((4-hydroxyphenyl)(phenyl)methylene)naphthalene-1-sulfono hydrazide), 10 (2''-chloro-N'-((4'-hydroxyphenyl)(phenyl)methylene)benzenesulfonohydrazide), 12 (N'-((4'-hydroxyphenyl)(phenyl)methylene)benzenesulfonohydrazide) have found to be potently active having an IC₅₀ value in the range of 3.90-17.99 µM. These compounds showed superior activity than standard acetohydroxamic acid (IC₅₀ = 29.20 ± 1.01 µM). Moreover, in silico studies on most active compounds were also performed to understand the binding interaction of most active compounds with active sites of urease enzyme. Structures of all the synthetic compounds were elucidated by ¹H NMR, ¹³C NMR, EI-MS and FAB-MS spectroscopic techniques.

Keywords: Benzophenone sulfonamide hybrid; In silico; In vitro; Urease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Benzophenones / chemical synthesis
Benzophenones / chemistry*
Benzophenones / pharmacology*
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology*
Inhibitory Concentration 50
Molecular Docking Simulation
Sporosarcina / drug effects
Sporosarcina / enzymology*
Structure-Activity Relationship
Sulfonamides / chemical synthesis
Sulfonamides / chemistry
Sulfonamides / pharmacology
Urease / antagonists & inhibitors*
Urease / metabolism

Substances

Benzophenones
Enzyme Inhibitors
Sulfonamides
Urease

Supplementary concepts

Sporosarcina pasteurii