In Silico ADME/T Properties of Quinine Derivatives using SwissADME and pkCSM Webservers
Jean Gonfi M. Mvondo
Department of Chemistry, Faculty of Sciences, University of Kinshasa, P.O Box 190, Kinshasa XI, Democratic Republic of the Congo.
Aristote Matondo *
Department of Chemistry, Faculty of Sciences, University of Kinshasa, P.O Box 190, Kinshasa XI, Democratic Republic of the Congo.
Dani T. Mawete
Department of Chemistry, Faculty of Sciences, University of Kinshasa, P.O Box 190, Kinshasa XI, Democratic Republic of the Congo.
Sylvie-Mireille N. Bambi
Department of Basic Sciences, Faculty of Pharmaceutical Sciences, University of Kinshasa, P.O Box 212, Kinshasa XI, Democratic Republic of the Congo.
Blaise M. Mbala
Department of Chemistry, Faculty of Sciences, University of Kinshasa, P.O Box 190, Kinshasa XI, Democratic Republic of the Congo.
Pierre O. Lohohola
Department of Chemistry, Faculty of Sciences, University of Kinshasa, P.O Box 190, Kinshasa XI, Democratic Republic of the Congo.
*Author to whom correspondence should be addressed.
Abstract
Aim: Malaria is among the most devastating and widespread tropical parasitic diseases. To overcome antimalarial drug resistance, new drugs need to be developed. This study is designed to establish the pharmacokinetic profile and toxicity of nine quinine derivatives as potential antimalarial drugs using in silico approaches by SwissADME and pkCSM.
Methodology: The structures of investigated compounds were translated into canonical SMILES format and then submitted to SwissADME web tool that gives free access to physicochemical properties, pharmacokinetics, drug-likeness and medicinal chemistry friendliness of compounds, and pkCSM webserver for predicting and optimizing pharmacokinetic and toxicity properties.
Results: SwissADME mainly used to predict the physicochemical properties of compounds and their drug-likeness revealed that all quinine derivatives have good bioavailability and satisfied the Lipinski’s rule of five. The pkCSM results on the absorption, distribution, metabolism, excretion and toxicity show that all investigated compounds have a good pharmacokinetic profile and they are safe since they belong to class 4 of the Globally Harmonized System (300 < Category 4 ≤ 2000 mg/kg/day).
Conclusion: Drug-likeness and ADME/T predictions of nine investigated quinine derivatives revealed that they are good candidates to oral drug formulation and thus they can be used in a broader context of overcoming the development of resistance by Plasmodium protozoans against most of the drugs currently used to treat malaria. As future prospects, further studies on bioevaluation of compounds are needed to elucidate their potential pharmacological activities.
Keywords: Quinine derivatives, malaria, pharmacokinetic profile, SwissADME, pkCSM