Molecular modeling studies of some phytoligands from Ficus sycomorus fraction as potential inhibitors of cytochrome CYP6P3 enzyme of Anopheles coluzzii

The major obstacle in controlling malaria is the mosquito’s resistance to insecticides, including pyrethroids. mainly due over-expression of detoxification enzymes such as cytochromes. Insecticides tolerance can be reduced by inhibitors P450s involved insecticide detoxification. Here, design potential CYP6P3 inhibitors, a homology model enzyme was constructed using crystal structure retinoic acid-bound cyanobacterial CYP120A1 (PDB ID: 2VE3; Resolution: 2.1 Å). Molecular docking study and computational modeling were employed determine inhibitory potentials some phytoligands isolated from Ficus sycomorus against Anopheles coluzzii modeled P450 isoforms, CYP6P3, implicated resistance. Potential ligand optimization (LE) properties analyzed standard mathematical models. Compounds 5, 8,and 9 bound Heme iron within 3.14, 2.47 2.59 Å, respectively. Their respective binding energies estimated -8.93, -10.44, -12.56 Kcal/mol. To examine stability their mode, resulting complexes these compounds with subjected 50 ns MD simulation. remained Fe (Heme):O (Ligand) distance appeared maintained over time. coordination strong heme shifts high- stable low-spin form prevented oxygen thereby inhibiting catalytic activity. LE index showed high (5 8) provide core fragment for into potent inhibitors.