article · Scientific African
Malaria, caused by the parasite Plasmodium falciparum, causes over one million deaths every year. Growing parasite resistance to established therapies such as chloroquine, artemisinin, and quinine has created an urgent requirement for novel treatments operating through alternative biological targets. To address this, twenty-four chemical derivatives of beta-amino alcohol grafted 1,4,5-trisubstituted 1,2,3-triazoles were evaluated through computational docking against the p53 protein, alongside assessments of their drug-likeness and ADMET profiles. Among these candidates, a specific derivative designated compound 10 demonstrated the greatest stability, yielding a re-rank docking score of -100.295 kilojoules per mole. Overall, the evaluated compounds broadly conformed to Lipinski rules for drug-likeness and exhibited favourable absorption, distribution, metabolism, and excretion characteristics. These computational findings offer a baseline to guide future structural optimisation of compound 10 derivatives to enhance p53 interactions and achieve effective parasite inhibition.
Widespread resistance to standard antimalarial medicines threatens global efforts to control Plasmodium falciparum infections, which claim over a million lives annually. Discovering new compounds that act on novel pathways is essential for developing next-generation treatments. Computational docking and pharmacological screening accelerate this process by identifying promising candidates with suitable absorption, distribution, and metabolic traits prior to costly physical laboratory testing.
This work represents very early-stage computational drug discovery. The findings could guide pharmaceutical researchers and medicinal chemists seeking to design and optimise new antimalarial candidate molecules based on the compound 10 scaffold. However, because the study is limited strictly to in-silico modelling without laboratory synthesis or biological assays, the compounds remain far from real-world therapeutic application.
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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.
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DOI: 10.1016/j.sciaf.2020.e00570
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