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Research highlights The research aimed at screening of the antimalarial derivatives of 2-anilino 4-amino substituted quinazolines docked against a Pf-DHODH protein target. Hence, some of the highlights are listed below: 1. The developed derivatives were discovered to follow Lipinski's rule of five in all of their properties, making them appropriate for drug treatment. 2. ADME pharmacokinetic properties of the designed derivatives were studied to know the oral bioavailability of the derivatives. 3. The ADME predictions shows the skin permeability of the derivatives to be within the tolerances level, as was their molar refractivity value. 4. The derivatives show high gastrointestinal absorptions in all the derivatives except in derivatives C-01, C-06, C-09, and C-10. 5. The designed derivatives may use in the treatment of other form of malarial with the exception of cerebral malaria since they lack BBB penetration. 6. Furthermore, the docking studies conducted shows Pf-DHODH to binds excellently with the designed ligands. 7. Derivative C-02, {5-((6,7-dimethoxy-4-((3-nitrobenzyl)amino)quinazolin-2-yl)amino)-2-fluorobenzaldehyde} (highest re-rank score and interaction energy of − 173.528 kcal/mol and an interaction energy of − 225.112 kcal/mol, respectively), was identified as the most stable of the designed derivatives. 8. The derivative C-04, N4-(3-chloro-5-fluorobenzyl)-N2-(4-fluorophenyl)-6,7-dimethoxyquinazoline-2,4-diamine, was found to be the least stable with − 120.489 and − 191.98 kcal/mol re-rank score and interaction energy, respectively. 9. Derivative C-02 binds with various amino acid residues such as Gly277, Phe278, Asn347, Lys429, Gly506, twice with Ile508, and Ala225 to produce eight (8) conventional hydrogen bonds with bonds lengths 2.7238 Å, 2.4607 Å, 2.3411 Å, 2.3244 Å, 2.0826 Å, 2.9660 Å, 2.0304 Å, and 2.6270 Å, respectively, in addition to two (2) carbon hydrogen bonds with Gly478 and Gly507 with bond distances of 2.4691 and 2.7052 Å, respectively. 10. The dynamic simulations results shows derivative C-02 forms a stable complex with the protein target. |
