Molecular docking studies, drug-likeness and in-silico ADMET prediction of some novel β-Amino alcohol grafted 1,4,5-trisubstituted 1,2,3-triazoles derivatives as elevators of p53 protein levels

Abstract

Malaria is a killer disease caused by Plasmodium falciparum and is responsible for over a million death annually. Chloroquine, quinine, pyrimethamine, proguanil, artemisinin, atovaquone, and mefloquine are different kinds of drugs employed to treat the disease, but due to increased drug resistance to these drugs, their use becomes less effective. Hence, the need for new antimalarial drugs with better activities and a new mechanism of action along different pathways against a new target. As well as the knowledge of their interactions, the drug-likeness of antimalarial drugs is necessary. Twenty-four derivatives of β-Amino alcohol grafted 1,4,5-trisubstituted 1,2,3-triazoles were docked against a p53 protein, as well as predicting their drug-likeness and ADMET properties. From the docking analysis, compound 10, {1-(1-benzyl-5-phenyl-1H-1,2,3-triazol-4-yl)-1-(4-bromophenyl)-2-((3,4-dimethylphenyl)amino)ethanol} was found to be the most stable compound with Re-rank docking score -100.295KJmol−1 against p53 protein. The “drug-likeness” and ADMET prediction performed nearly showed compliance with the Lipinski rule, and the compounds were found to have good absorption, distribution, metabolism, and excretion generally. The results of the study can be used for future optimization of derivatives of {1-(1-benzyl-5-phenyl-1H-1,2,3-triazol-4-yl)-1-(4-bromophenyl)-2-((3,4-dimethylphenyl)amino)ethanol}for better molecular interactions with p53 protein, and effective Plasmodium falciparum inhibition.