Exploring the efficacy of new potential bio-insecticides produced by Penicillium oxalicum against Culex pipiens larvae

Synthetic insecticides are major contributors to environmental pollution and the emergence of resistance. Fungal-derived metabolites are known to be environmentally friendly, selective alternatives. Thus, in the context of a green environment, this study aimed to evaluate the larvicidal activity of a mangrove-associated endophytic Penicillium oxalicum (OQ231606.1) against Culex pipiens using a larval mortality bioassay and molecular docking. The culture filtrate extract of the examined P. oxalicum OQ231606.1 strain caused up to 80% mortality (optimized to 99.98%). Metabolite production conditions were optimized using a full factorial design followed by a central composite design. Optimum conditions were pH 6, 1.2 × 106 spores/mL inoculum, 28 °C, for 20 days. Physcion and deoxybrevianamide E, two bioactive compounds with newly reported biolarvicidal activity, were isolated from the fungal extract and structurally elucidated via NMR spectroscopy. C. pipiens third-instar larvae treated with various concentrations of these compounds showed increased mortality with increasing concentrations. Notably, deoxybrevianamide E was more potent, with an LC₅₀ value less than 1 µg/mL at 48 h (LC50 = 0.84 µg/mL vs. Physcion’s = 12.64 µg/mL). Docking analysis revealed potential insect receptors interacting with candidate compounds, showing deoxybrevianamide E and okaramine B (control) share the same active site, targeting glutamate-gated chloride channel (GluCl) with binding affinities of − 9.5 Kcal/mol and − 9.1 Kcal/mol, respectively. Whereas physcion and emodin (control) target acetylcholinesterase (AChE), with binding affinities of − 8.5 Kcal/mol and − 8.9 Kcal/mol, respectively. This study highlights P. oxalicum OQ231606.1 as a sustainable reservoir for bioinsecticide development, identifying physcion and deoxybrevanamide E as bioactive compounds with newly reported biolarvicidal activity that represent promising candidates for green vector control strategies.