Computational approach by molecular docking and molecular dynamics of compounds from two Congolese medicinal plants as potent antisickling agents - 2026
[en] Background: Sickle cell disease is a genetic disorder caused by hemoglobin S, and its treatment remains challenging. Compounds that penetrate erythrocytes to stabilize hemoglobin S are potential therapeutic agents. This study evaluated the in silico antisickling activity of 13 isolated flavonoids from Justicia secunda and Moringa oleifera using molecular docking and dynamics. Methods: Deoxyhemoglobin (3WCU) and human bisphosphoglycerate mutase (3NFY) were used as receptor proteins. Flavonoids were identified via LC-MS/MS in positive and negative modes. Frontier molecular orbital (FMO) analysis, QSAR studies, ADMET profiling, and molecular dynamics simulations (MD) were conducted to assess reactivity, stability, and drug-likeness. Results: Four compounds (C_3, C_9, C_11, C_12) showed the highest docking activity, with C_11 and C_12 emerging as top ligands. FMO analysis indicated HOMO energies (–5.496 to –5.917 eV) and LUMO energies (–1.139 to –1.468 eV). Water solubility, GI absorption, BBB permeability, and CYP interactions were predicted, with all compounds classified as soluble but low GI absorption and non-BBB permeant. Drug-likeness evaluation showed multiple violations, typical for large flavonoids, while bioavailability scores were 0.17. Medicinal chemistry filters revealed minimal PAINS/Brenk alerts with synthetic accessibility ranging 3.82–7.42. Docking and hydrogen-bond analyses indicated that C_11 and C_12 interacted with key residues of 3WCU and 3NFY. MD simulations and ADMET profiles confirmed the stability and drug-like potential of C_11 and C_12 as promising in silico leads. Conclusion: In silico analyses suggest that C_11 and C_12 are promising candidates for antisickling drug development, supported by binding affinity, molecular stability, hydrogen-bond interactions, and favorable quantum chemical, physico-chemical, and pharmacokinetic properties.
Disciplines :
Alternative medicine Pharmacy, pharmacology & toxicology
Author, co-author :
Gbolo, Benjamin Z. ; Department of Biology, Faculty of Sciences, University of Kinshasa, Kinshasa XI, Democratic Republic Congo ; Unit of Therapeutic Chemistry and Pharmacognosy, Faculty of Medicine and Pharmacy, University of Mons (UMONS), Mons, Belgium
Eltayb, Wafa Ali ; Biotechnology Department, Faculty of Science and Technology, Shendi University, Shendi, Sudan
Ngbolua, K.N. ; Department of Biology, Faculty of Sciences, University of Kinshasa, Kinshasa XI, Democratic Republic Congo
Shabana, Samah ; Department of Biochemistry and Molecular Biology, College of Marine Life Sciences, Ocean University of China, Qingdao, China
Semay, Irène ; Université de Mons - UMONS > Faculté des Sciences > Service de Synthèse et spectrométrie de masse organiques
Hamouda, Hamed I. ; Processes Development Department, EPRI, Nasr City, Egypt
Gerbaux, Pascal ; Université de Mons - UMONS > Faculté des Sciences > Service de Synthèse et spectrométrie de masse organiques
Mohsen, Mohamed ; Fish Production Department, Faculty of Agriculture, Al-Azhar University, Nasr City, Egypt
Kitete, Emmanuel M. ; Department of Chemistry, Faculty of Sciences, University of Kinshasa, Kinshasa XI, Democratic Republic Congo
Mpiana, Pius T. ; Department of Chemistry, Faculty of Sciences, University of Kinshasa, Kinshasa XI, Democratic Republic Congo
Wang, Xiling ; CAS Key Laboratory of Biofuels and Shandong Provincial Key Laboratory of Synthetic Biology, Qingdao Institute of Bioenergy and Bioprocess Technology Chinese Academy of Sciences, Qingdao, China
Duez, Pierre ; Université de Mons - UMONS > Faculté de Médecine, Pharmacie et Sciences Biomédicales > Service de Chimie thérapeutique et Pharmacognosie
Abdalla, Mohnad ; Pediatric Research Institute, Children's Hospital Affiliated to Shandong University, Jinan, China
M136 - Chimie thérapeutique et Pharmacognosie S836 - Synthèse et spectrométrie de masse organiques
Research institute :
R550 - Institut des Sciences et Technologies de la Santé R100 - Institut des Biosciences
Funders :
ARES CCD - Académie de Recherche et d'Enseignement Supérieur. Coopération au Développement
Funding text :
This project was carried out thanks to funding of the Academy of Research and Higher Education (ARES), Grant number: COOP-CONV-18\u2013004, AI ARES UNIKIN, of which Mr. Gbolo was the main beneficiary.
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