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Background Leishmaniasis is a neglected tropical disease caused by a group of protozoan of the genus  Leishmani a and transmitted to humans majorly through the bite of the female sand fly. It is prevalent in the tropical regions of the world especially in Africa and estimated to affect a population of about 12 million people annually. This theoretical study was therefore conducted in support of the search for more effective drug candidates for the treatment of leishmaniasis. This study focuses on the in silico activity prediction of twenty-eight (28) maleimides, structure-based design, molecular docking study and pharmacokinetics analysis of the newly designed maleimides. All the studied compounds were drawn using ChemDraw Ultra and optimized by the density functional theory (DFT) approach using B3LYP with 6-31G⁄ basis set. Results The built QSAR model was found to satisfy the requirement of both internal and external validation tests for an acceptable QSAR model with  R  2  = 0.801,  R  2  adj  = 0.748,  Q  2  cv  = 0.710,  R  2  test  = 0.892 and c R  p  2  = 0.664 and has shown excellent prediction of the studied compounds. Among the five (5) protein receptors utilized for the virtual docking screening, pyridoxal kinase (PdxK) receptor (Pdb id = 6k91) showed the strongest binding interactions with compounds  14 ,  21  and  24  with the highest binding affinities of − 7.7, − 7.7 and − 7.8 kcal/mol, respectively. The selected templates ( 14 ,  21  and  24 ) were used to design twelve (12) new compounds (N1–N12) with higher docking scores than the templates.  N7  (affinity =  − 8.9 kcal/mol) and  N12  (− 8.5 kcal/mol) showed higher binding scores than the reference drug pentamidine (− 8.10 kcal/mol), while  N3  and  N7 – N12  showed higher predicted pIC 50  than the templates. Also, the pharmacokinetics properties prediction revealed that the newly designed compounds, obeyed the Lipinski’s rule for oral bio-availability, showed high human intestinal absorption (HIA), low synthetic accessibility score, CNS and BBB permeability and were pharmacologically active. Conclusions The activities of the various maleimides were predicted excellently by the built QSAR model. Based on the pharmacokinetics and molecular docking studies therefore, the newly designed compounds are suggested for further practical evaluation and/or validation as potential drug candidates for the treatment of leishmaniasis.

bulletin of the national research centre/bulletin of the national research center

Theoretical activity prediction, structure-based design, molecular docking and pharmacokinetic studies of some maleimides against Leishmania donovani for the treatment of leishmaniasis