Selective modification of diclofenac to reduce the adverse effects; A computer-aided drug design approach

• DOI: 10.1016/j.imu.2023.101159
• Publication Date: 2023-01-03T00:22:57Z
• Authors: Md. Kamrul Hasan; Shamima Akhter; Kaniz Fatema; Md. Rezaul Hossain; Tamanna Sultana; Monir Uzzaman
• Keywords: Diclofenac; Docking (animal); Drug Design

Diclofenac (DCF) is a non-steroidal anti-inflammatory drug (NSAID), commonly used for the treatment of pain. It can inhibit prostaglandin synthesis by blocking cyclooxygenase (COX). shows some crucial side effects like gastrointestinal, cardiovascular, renal, and liver injury. The gastrointestinal injury occurred due to presence carboxylic (COOH) group at core DCF. hydroxyl (OH) portion COOH was replaced inserting new functional groups (CH3, OCH3, CH2NH2, NH2, NHCOCH3, NHCONH2, Cl, CF3) considering retrosynthetic strategy which reduces with improved chemical biological activity. Herein, we have investigated physicochemical, spectral, molecular dynamics, pharmacokinetic properties mentioned analogues. Density theory (DFT) time-dependent DFT along B3LYP/6-31g (d,p) basis set been utilized calculate their geometrical, chemical, spectral properties. Molecular docking non-bonding interactions performed against human synthase protein (PDB ID: 5F1A) investigate binding affinities, modes, stability. ADMET PASS prediction studies were microbial inhibition toxicological profile. Quantum calculations characterization support geometry newly designed From simulation, most analogues exhibited better affinity than parent except DCF-2. predict non-carcinogenic all DCF Biological activities drug-likeness indicate that exposed comparatively lower action hemorrhage exhibit antipyretic, analgesic, actions as well overcome poor absorption or permeation drugs. Finally, based on above investigation, this study be helpful design potential candidate medicinal reduced selective adverse effects.