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

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). It shows some crucial side effects like gastrointestinal, cardiovascular, renal, and liver injury. The gastrointestinal injury occurred due to the presence of a carboxylic (COOH) group at the core of DCF. The hydroxyl (OH) portion of COOH was replaced by inserting some new functional groups (CH3, OCH3, CH2NH2, NH2, NHCOCH3, NHCONH2, Cl, CF3) considering the retrosynthetic strategy which reduces gastrointestinal side effects with improved chemical and biological activity. Herein, we have investigated the physicochemical, spectral, molecular dynamics, biological and pharmacokinetic properties of the mentioned analogues. Density functional theory (DFT) and time-dependent DFT along with the B3LYP/6-31g…