Medicinal chemistry (Shariqah (United Arab Emirates)) · 2026
In silico and in vitro Analysis of Secondary Metabolites of Pleurotus djamor Against Targets of Haemonchus contortus.
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Ortiz-Perez Eyra, Quintero-Solano Jose M, Pineda-Alegría Jesús Antonio, Robles-Inclan Fernanda, Aguilar-Marcelino Liliana, Rivera Gildardo
Аннотация
INTRODUCTION/OBJECTIVE: Haemonchosis is a gastrointestinal disease caused by the nematode Haemonchus contortus, a serious problem in sheep farming worldwide. Benzimidazole drugs are used as treatment; however, their ineffectiveness and resistant strains indicate a need for new therapeutic options. Therefore, this project aimed to determine the possible mode of action and nematicidal activity of secondary metabolites of the mushroom Pleurotus djamor against H. contortus.
METHODS: Four pharmacological targets were selected to assess the binding affinity of the major secondary metabolites by molecular docking and molecular dynamics simulations. Subsequently, the nematicidal activity of selected compounds was evaluated using larval mortality assays.
RESULTS: Molecular docking analysis determined an affinity of 5,6-dimethoxy-1(3H)-isobenzofuranone (DIB) and veratryl alcohol (VA) for phosphoethanolamine N-methyltransferase (PMT1 and PMT2). Nevertheless, molecular dynamics simulations revealed that only the PMT1-DIB complex displayed greater stability than the control. In the in vitro evaluation, VA induced dose-dependent larval mortality, reaching 55% at 5 mg/mL, while CAF was inactive. No synergistic effect was observed with the combination of VA and CAF.
DISCUSSION: The stable interaction observed between DIB and PMT1 suggests that this enzyme may represent a promising anthelmintic target in H. contortus. In contrast, the biological activity exhibited by VA despite its unstable binding profile indicates the possible involvement of alternative molecular targets or pathways. Nevertheless, additional biochemical and experimental studies are required to further elucidate the underlying mechanisms of action.
CONCLUSION: These findings highlight PMT1 as a promising pharmacological target and suggest that DIB and VA may contribute to the anthelmintic activity of P. djamor metabolites against H. contortus.
METHODS: Four pharmacological targets were selected to assess the binding affinity of the major secondary metabolites by molecular docking and molecular dynamics simulations. Subsequently, the nematicidal activity of selected compounds was evaluated using larval mortality assays.
RESULTS: Molecular docking analysis determined an affinity of 5,6-dimethoxy-1(3H)-isobenzofuranone (DIB) and veratryl alcohol (VA) for phosphoethanolamine N-methyltransferase (PMT1 and PMT2). Nevertheless, molecular dynamics simulations revealed that only the PMT1-DIB complex displayed greater stability than the control. In the in vitro evaluation, VA induced dose-dependent larval mortality, reaching 55% at 5 mg/mL, while CAF was inactive. No synergistic effect was observed with the combination of VA and CAF.
DISCUSSION: The stable interaction observed between DIB and PMT1 suggests that this enzyme may represent a promising anthelmintic target in H. contortus. In contrast, the biological activity exhibited by VA despite its unstable binding profile indicates the possible involvement of alternative molecular targets or pathways. Nevertheless, additional biochemical and experimental studies are required to further elucidate the underlying mechanisms of action.
CONCLUSION: These findings highlight PMT1 as a promising pharmacological target and suggest that DIB and VA may contribute to the anthelmintic activity of P. djamor metabolites against H. contortus.