Computer aid screening for potential antimalarial choroquinone compounds as covid 19 utilizing computational calculations and molecular docking study

Abstract

Click reaction of 4,7-dichloroquinoline (1) with thiosemicarbazide (2) to afford the corresponding 2-(7-chloroquinolin-4-yl)thiosemicarbazide (3) utilized ultrasonic irradiation which can cyclized easily with ethylacetoacetate to give the 3-(7-chloroquinolin-4-ylamino)-tetrahydro-6-methyl-2-thioxopyrimidin-4(1H)-one (4) via nucleophilic substitution reaction. The synthesized compounds was examined in vitro antimalarial activity with IC50 = 11.92, 25.37 μg/mL against chloroquinone drug. Furthermore, the theoretical investigation of most active compounds CQT and CQP utilizing of DFT/B3LYP/6-311G(d) and HF/6-311G(d) basis’s set and evaluated their physical characters, bond length, bond angles, dihedral angles, also its HOMO-LUMO energy gap was 3.77 eV which indicate the reactivity of CQP. Moreover, the molecular docking studies of these synthesized compounds showed small energy affinity against SARS-CoV-2 main protease (PDBID: 6lu7) and crystal structure of thermoplasma acidophilum (PDBID: 1q2w) and shorter bond length. All these parameters could be considered with different extent to significantly affect the binding affinity of these compounds to the active protein sites for further biological evaluation on Covid-19.