title: Inhibition and Larvicidal Activity of Phenylpropanoids from Piper sarmentosum on Acetylcholinesterase against Mosquito Vectors and Their Binding Mode of Interaction.
abstract: Aedes aegypti, Aedes albopictus and Culex quinquefasciatus are vectors of dengue fever and West Nile virus diseases. This study was conducted to determine the toxicity, mechanism of action and the binding interaction of three active phenylpropanoids from Piper sarmentosum (Piperaceae) toward late 3rd or early 4th larvae of above vectors. A bioassay guided-fractionation on the hexane extract from the roots of Piper sarmentosum led to the isolation and identification of three active phenylpropanoids; asaricin 1, isoasarone 2 and trans-asarone 3. The current study involved evaluation of the toxicity and acetylcholinesterase (AChE) inhibition of these compounds against Aedes aegypti, Aedes albopictus and Culex quinquefasciatus larvae. Asaricin 1 and isoasarone 2 were highly potent against Aedes aegypti, Aedes albopictus and Culex quinquefasciatus larvae causing up to 100% mortality at ≤ 15 μg/mL concentration. The ovicidal activity of asaricin 1, isoasarone 2 and trans-asarone 3 were evaluated through egg hatching. Asaricin 1 and isoasarone 2 showed potent ovicidal activity. Ovicidal activity for both compounds was up to 95% at 25μg/mL. Asaricin 1 and isoasarone 2 showed strong inhibition on acetylcholinesterase with relative IC50 values of 0.73 to 1.87 μg/mL respectively. These findings coupled with the high AChE inhibition may suggest that asaricin 1 and isoasarone 2 are neuron toxic compounds toward Aedes aegypti, Aedes albopictus and Culex quinquefasciatus. Further computational docking with Autodock Vina elaborates the possible interaction of asaricin 1 and isoasarone 2 with three possible binding sites of AChE which includes catalytic triads (CAS: S238, E367, H480), the peripheral sites (PAS: E72, W271) and anionic binding site (W83). The binding affinity of asaricin 1 and isoasarone 2 were relatively strong with asaricin 1 showed a higher binding affinity in the anionic pocket.
authors.affiliation: Institute of Biological Sciences, Faculty of Science Building, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Arshia
authors.initials: A
authors.lastname: Hematpoor
authors.affiliation: Department of Chemistry, Faculty of science, University of Malaya, Kuala Lumpur, Malaysia.|Centre for Natural Products and Drug Discovery (CENAR), University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Sook Yee
authors.initials: SY
authors.lastname: Liew
authors.affiliation: Department of Chemistry, Faculty of science, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Wei Lim
authors.initials: WL
authors.lastname: Chong
authors.affiliation: Institute of Biological Sciences, Faculty of Science Building, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Mohd Sofian
authors.initials: MS
authors.lastname: Azirun
authors.affiliation: Department of Chemistry, Faculty of science, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Vannajan Sanghiran
authors.initials: VS
authors.lastname: Lee
authors.affiliation: Department of Chemistry, Faculty of science, University of Malaya, Kuala Lumpur, Malaysia.|Centre for Natural Products and Drug Discovery (CENAR), University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Khalijah
authors.initials: K
authors.lastname: Awang
mesh_terms: D000110:Acetylcholinesterase / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002800:Cholinesterase Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D007302:Insect Repellents / Q000494:pharmacology; D007814:Larva / Q000187:drug effects*; D013058:Mass Spectrometry; D062105:Molecular Docking Simulation; D000072138:Mosquito Vectors / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D010666:Phenylpropionates / Q000378:metabolism / Q000494:pharmacology*; D031701:Piper / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy
chemical_list: D002800:Cholinesterase Inhibitors; D007302:Insect Repellents; D010666:Phenylpropionates; D000110:Acetylcholinesterase