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

dc.authorscopusid57222297921
dc.authorscopusid24830377800
dc.authorscopusid6506307348
dc.authorscopusid6506158277
dc.authorscopusid57038704300
dc.contributor.authorYelekçi, Kemal
dc.contributor.authorAnosike, C.A.
dc.contributor.authorEzeanyika, L.U.S.
dc.contributor.authorYelekçi, K.
dc.contributor.authorUba, A.I.
dc.date.accessioned2023-10-19T15:05:21Z
dc.date.available2023-10-19T15:05:21Z
dc.date.issued2022
dc.department-tempBabandi, A., Department of Biochemistry, Bayero University, Nigeria, Department of Biochemistry, University of Nigeria, Nsukka, Nigeria; Anosike, C.A., Department of Biochemistry, University of Nigeria, Nsukka, Nigeria; Ezeanyika, L.U.S., Department of Biochemistry, University of Nigeria, Nsukka, Nigeria; Yelekçi, K., Department of Bioinformatics and Genetics, Faculty of Engineering and Natural Science, Kadir Has University, Turkey; Uba, A.I., Complex Systems Division, Beijing Computational Science Research Center, Chinaen_US
dc.description.abstractThe major obstacle in controlling malaria is the mosquito’s resistance to insecticides, including pyrethroids. The resistance is mainly due to the over-expression of detoxification enzymes such as cytochromes. Insecticides tolerance can be reduced by inhibitors of P450s involved in insecticide detoxification. Here, to design potential CYP6P3 inhibitors, a homology model of the enzyme was constructed using the crystal structure of retinoic acid-bound cyanobacterial CYP120A1 (PDB ID: 2VE3; Resolution: 2.1 Å). Molecular docking study and computational modeling were employed to determine the inhibitory potentials of some phytoligands isolated from Ficus sycomorus against Anopheles coluzzii modeled P450 isoforms, CYP6P3, implicated in resistance. Potential ligand optimization (LE) properties were analyzed using standard mathematical models. Compounds 5, 8,and 9 bound to the Heme iron of CYP6P3 within 3.14, 2.47 and 2.59 Å, respectively. Their respective binding energies were estimated to be-8.93,-10.44, and-12.56 Kcal/mol. To examine the stability of their binding mode, the resulting docking complexes of these compounds with CYP6P3 were subjected to 50 ns MD simulation. The compounds remained bound to the enzyme and Fe (Heme):O (Ligand) distance appeared to be maintained over time. The coordination of a strong ligand to the heme iron shifts the iron from the high-to the stable low-spin form and prevented oxygen from binding to the heme thereby inhibiting the catalytic activity. The LE index showed the high potential of these compounds (5 and 8) to provide a core fragment for optimization into potent P450 inhibitors. © 2022 DSR Publishers/The University of Jordan. All Rights Reserved.en_US
dc.description.sponsorshipThe authors were grateful to Tetfund for financially supporting the project.en_US
dc.identifier.citation4
dc.identifier.endpage275en_US
dc.identifier.issn1995-7157
dc.identifier.issue2en_US
dc.identifier.scopus2-s2.0-85133010734en_US
dc.identifier.scopusqualityQ3
dc.identifier.startpage258en_US
dc.identifier.urihttps://hdl.handle.net/20.500.12469/4846
dc.identifier.volume15en_US
dc.identifier.wosqualityN/A
dc.khas20231019-Scopusen_US
dc.language.isoenen_US
dc.publisherUniversity of Jordan,Deanship of Scientific Researchen_US
dc.relation.ispartofJordan Journal of Pharmaceutical Sciencesen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectCYP6P3en_US
dc.subjectCYP6P3 inhibitorsen_US
dc.subjectHomology modelingen_US
dc.subjectMolecular dockingen_US
dc.subjectMolecular dynamics simulation ligand efficiencyen_US
dc.subjectcytochrome P450en_US
dc.subjectglutamic aciden_US
dc.subjectironen_US
dc.subjectliganden_US
dc.subjectoxygenen_US
dc.subjectretinoic aciden_US
dc.subjectzincen_US
dc.subjectamino acid sequenceen_US
dc.subjectAnophelesen_US
dc.subjectAnopheles coluzziien_US
dc.subjectArticleen_US
dc.subjectbinding affinityen_US
dc.subjectbinding siteen_US
dc.subjectblood brain barrieren_US
dc.subjectcontrolled studyen_US
dc.subjectcrystal structureen_US
dc.subjectdetoxificationen_US
dc.subjectDNA bindingen_US
dc.subjectenzyme active siteen_US
dc.subjectenzyme bindingen_US
dc.subjectFicusen_US
dc.subjecthydrogen bonden_US
dc.subjectinhibition constanten_US
dc.subjectligand bindingen_US
dc.subjectlipophilicityen_US
dc.subjectmathematical modelen_US
dc.subjectmolecular dynamicsen_US
dc.subjectmolecular modelen_US
dc.subjectnonhumanen_US
dc.subjectpharmacophoreen_US
dc.subjectquantitative structure activity relationen_US
dc.subjectsimulationen_US
dc.subjectthermodynamicsen_US
dc.subjectvalidation processen_US
dc.subjectX ray crystallographyen_US
dc.titleMolecular modeling studies of some phytoligands from Ficus sycomorus fraction as potential inhibitors of cytochrome CYP6P3 enzyme of Anopheles coluzziien_US
dc.typeArticleen_US
dspace.entity.typePublication
relation.isAuthorOfPublication9407938e-3d31-453b-9199-aaa8280a66c5
relation.isAuthorOfPublication.latestForDiscovery9407938e-3d31-453b-9199-aaa8280a66c5

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