1Nawaf Abubakar, 2Haruna Y. Ismail, 3Kaumi Alkali and 1Mohammed Mustapha Mohammed
1Department of Applied Biology, Federal University of Technology Babura, Jigawa State.
2Department of Microbiology, Faculty of Life Sciences, University of Maiduguri, Borno State
3Department of Biological Sciences. Al-Ansar University Maiduguri, Borno State
*Corresponding author’s Email: yismailh@gmail.com, doi.org/10.55639/607.02010047
ABSTRACT
This study explored essential oil-derived compounds from Nigella sativa as inhibitors of insecticide-resistant acetylcholinesterase (AChE1) from Anopheles gambiae, a key malaria vector. A library of 132 phytochemicals retrieved from the LOTUS database was subjected to screening for physicochemical properties, pharmacokinetics, and drug-likeness using SwissADME. Only four compounds met combined criteria for molecular weight, hydrogen bonding potential, topological polar surface area, and predicted gastrointestinal absorption, alongside minimal interference with cytochrome P450 enzymes. These candidates proceeded to molecular docking with the G119S-mutated AChE1 (PDB ID: 6ARX), linked to resistance against carbamate and organophosphate insecticides. Docking scores ranged from –6.90 kcal/mol to –9.60 kcal/mol. The strongest binder, CID:2005341, formed a hydrogen bond with Tyr282 and engaged multiple hydrophobic residues critical for active site stabilization. Other compounds showed varying combinations of hydrogen bonding and hydrophobic contacts with residues Ser283, Cys447, and Trp441. These results indicate the potential of selected N. sativa phytochemicals to inhibit the resistant AChE1 variant, which highlights them as promising candidates for developing plant-based agents to support vector control programs. Further work, including molecular dynamics simulations and biological assays, is recommended to confirm these findings and evaluate their suitability as biopesticide leads.
Keywords:
Nigella sativa,
Anopheles gambiae
Molecular docking,
Insecticide,
ADMET