Computational, Pharmacological Evaluation and Comparative Similarity against Chloroquine for Some New Designed Hybridized Molecules and their Potential Use as Antiviral against COVID-19 and Malaria

Abstract

Starting from the concept of "similar molecules exert similar biological activities" to modify structures of biologically active molecules or readily available drugs to improve their therapeutic activity or reduce side effects. Four designed 7- Chloroqunioline-N-Heterocyclic molecules that are derived from parent compound chloroquine (which recently has attracted wide international attention due to its potential activity against COVID-19) were investigated regarding QSAR and some electronic parameters compared to the original drug. Their chemical properties, biochemical properties, and physio-chemical properties were evaluated using computational chemistry. The method used for calculations was semi-empirical-geometry optimization-PM3. Single crystal X-ray crystallography data of Chloroquine and calculated data have been done using the same parameters. Surprisingly, the experimental and calculated data recorded the same values. Furthermore, in Silico evaluation of pharmacokinetics, drug-likeness and medicinal chemistry friendliness of four hybridized molecules compared to chloroquine by using SwissADME web tool confirm closeness of four hybrids to the chloroquine. The total energy, binding energy, dipole moment energy gap (HOMOLUMO) and log p of one of compounds coded AB1-4Py were -7.6647.710 Kcalmol-1, -3981.323, 4.531, 8.161 eV, and 4.25 respectively. AB2-4py compound calculated total energy was76007.6- , Binding energy at - 4109.424, dipole moment at 4.464, energy gap (EHOMO-ELUMO) at 8.131 and log p at 4.70. The AB1-4py, AB2-4py and chloroquine reported same stability and bioactivities. From QSAR study, the value of Log P indicates hydrophobic nature. The recorded values of AB1-4Py and AB2-4py were completely agreed with those of chloroquine. Therefore, this study may valuable in the discovery of a new series of potential drugs for treatment of malaria or COVID-19.