Theoretical Investigation on Reaction Pathway, Biological Activity, Toxicity and NLO Properties of Diclofenac Drug and Its Ionic Carriers

Mustafa M Kadhim,Rehab M Kubba

doi:10.24996/ijs.2020.61.5.1

Abstract

The present study included the use of the approximate semi-experimental method, the time-independent density function theory (unrestricted), the time-dependent density function theory, and Hartree-Fock method to calculate the reaction pathway of the anti-inflammatory drug diclofenac with its common ionic carriers (sodium and potassium). The basis sets used were STO-3G, 3-21G, 6-31G, and 6-311G. The drug was studied with two new proposed carrier ions (lithium and calcium) which were compared with common carriers. The calculations included the optimized geometrical structure and some physical properties such as standard heat of formation, dipole moment, total energies, and analytical spectra of IR, UV-VIS and 1H NMR. The biological and toxicological activities and the nonlinear optical (NLO) properties were also studied theoretically for the drug and for its proposed and common carriers. All calculations were performed using Gaussian-09 program. The results of the proposed carriers were compared with the common carriers in terms of activation energies, transition states, and products. This study is considered as a step to develop diclofenac prodrugs and find new carriers for diclofenac. The proposed lithium showed a good result and a potential for use as a drug carrier. The results also showed the convergence of the values of the common carriers (Na, K) and those of the proposed carrier (Ca), with their preference over it.

Highlights

Diclofenac is a non-steroidal anti-inflammatory drug (NSAID)
The possible way to solve this problem is to convert the carboxylic function to produce the prodrug with adequate stability at the acidic pH of the stomach. This may prevent the local damage of stomach mucosa, and it is capable of releasing the parent drug spontaneously or enzymatically in the blood following its absorption [3,4]
Using quantum mechanical calculations of semiempirical PM3 and Unrestricted Hartree-Fock (UHF) methods, Kubba et al studied the O-R bond rupture in some prodrug derivatives of ampicillin and cefuroxime, including different substituted organic groups, in an attempt to show which of them could be chosen as a functional carrier linkage for ampicillin or cefuroxime [23,24]

Summary

Introduction

Diclofenac is a non-steroidal anti-inflammatory drug (NSAID). It is used in the treatment of pain and symptoms of osteoarthritis. This research aims to study the reaction path curves for the carriers linkage rupture in standard diclofenac prodrugs and some of the new suggested ionic carriers, using the ab initio U-DFT and PM3 methods [25,26]. Table-1 shows the calculations of the bond lengths (Å) for the studied diclofenac prodrugs at their equilibrium geometries using PM3 and U-DFT methods.

Objectives

Results

Conclusion