Investigation of Pyrazole-Linked Carbonitrile-Based Schiff Bases through Molecular Dynamic Simulation As Promising Urease and Thymidine Phosphorylase Inhibitors: Synthesis in vitro Biological Screening, DFT and Computational Approaches

Hina Sarfraz

doi:10.1142/S2737416526500705

Investigation of Pyrazole-Linked Carbonitrile-Based Schiff Bases through Molecular Dynamic Simulation As Promising Urease and Thymidine Phosphorylase Inhibitors: Synthesis in vitro Biological Screening, DFT and Computational Approaches

2026-03-01

0

PRE

AI

H

Hina Sarfraz

Y

Yousaf Khan *

N

Naqvi, Syeda Farwa

H

Hussain, Rafaqat *

N

Naseem Bano

A

Azmat Ullah Khan

M

Maryyam Javed

N

Nawal H. Siddig

N

Nawal Al-Hoshani

M

Maher S. Alwethaynani

DOI：10.1142/S2737416526500705

Original

Original request for help

Save

Abstract

En 中文

Twelve new pyrazole-linked carbonitrile-based Schiff base derivatives have been prepared in the present study following a two-step pathway of reactions and tested as a dual inhibitor of urease and thymidine phosphorylase (TP). The main target of this study was to develop structurally simple yet biologically active pyrazole-based scaffolds for targeting enzymes involved in bacterial infections and cancer-related angiogenesis. The originality of this research lies in the rational synthesis of a pyrazole-carbonitrile core bearing Schiff base functionality, and in the thorough examination of the structure-activity relationship (SAR) through the in vitro, in silico and quantum chemical studies. The compounds synthesized were structurally verified by the use of the NMR spectroscopy of H-1 and (1)3C and screened against enzyme inhibition. Some of the derivatives showed better activity than the standard inhibitors, with compounds 4 (13.47 +/- 1.12 mu M for urease; 4.04 +/- 1.78 mu M for TP), 11 (14.75 +/- 1.53 mu M; 4.42 +/- 0.98 mu M), and 8 (17.93 +/- 1.98 mu M; 5.73 +/- 2.16 mu M). The results of molecular docking showed favorable binding interactions in the active sites of urease (PDB ID: 4UBP) and TP (PDB ID: 4EAD). In order to confirm binding stability, 100 ns molecular dynamics simulations were conducted, which confirmed stable ligand-protein complexes, especially between compound 8 and urease and compound 4 and TP. DFT calculations were used to understand electronic stability and reactivity, and ADME analysis identified drug-like properties acceptable for the lead compounds.

Keywords:

Pyrazole

carbonitrile

Schiff bases

molecular dynamics simulation

urease

thymidine phosphorylase

DFT

Investigation of Pyrazole-Linked Carbonitrile-Based Schiff Bases through Molecular Dynamic Simulation As Promising Urease and Thymidine Phosphorylase Inhibitors: Synthesis in vitro Biological Screening, DFT and Computational Approaches

Abstract

Journal

Organization

Cited Papers

Citing Papers