Exploring the Potential of bioactive compounds from Cordyceps sinensis known to infect Lepidoptera larvae as Antimalarial Agents through In silico studies
TL;DR
Eleven bioactive compounds from insect pathogenic fungi that infects larvae of Hepialus (Lepidoptera, ghost moths) were selected from previously reported literature and investigated for their potential antimalarial activity using molecular docking and pharmacokinetic analyses, demonstrating their potential as promising novel therapeutic candidates for the treatment of malaria.
Abstract
Malaria has been one of the most prevalent and life-threatening infectious disease worldwide. Despite extensive efforts to control and combat the disease, the emergence of drug resistant malaria parasites have posed a formidable obstacle in the fight against this deadly infection. Insect pathogenic fungi have emerged as a rich and important source of bioactive compounds with diverse pharmacological properties. Consequently, there is need to develop derivatives of bioactive compounds with antimalarial activity from insect pathogenic fungi with improved efficacies and better binding affinities than the existing drugs. Eleven bioactive compounds from insect pathogenic fungi, Cordyceps sinensis that infects larvae of Hepialus (Lepidoptera, ghost moths) were selected from previously reported literature and investigated for their potential antimalarial activity using molecular docking and pharmacokinetic analyses.. These compounds were docked using a model of Triosephosphate isomerase (TPI) protein with Molegro software to identify the compound with the minimum docking score as a design template. Compound 6 (3,5,8-trihydroxy-6-methoxy-2-((1E,3E)-5-oxohexa-1,3-dien-1-yl)naphthalene-1,4-dione) with the lowest moldock score (-112.711 kcal mol-1) was employed as the template. Derivatives were designed by substituting -COOH, -CONH2, -COOCH3, -CN, and -SO3H groups at various positions of the template where three of the designed derivatives had better binding affinities compared to the design template. The docking scores of these designed derivatives were lower than those of the original compounds. Derivative D3 (1,4,6-trihydroxy-3-methoxy-5,8-dioxo-7- ((1E,3E)-5-oxohexa-1,3-dien-1-yl)-5,8-dihydronaphthalene-2-carboxamide) was identified to bind better to the target protein due to its lowest moldock score (-118.325 kcal mol-1). The druglikeness assessment of the designed derivatives demonstrated that all compounds complied with Lipinski’s Rule of Five (Ro5), supporting their favourable drug-like properties and highlighting their potential as promising novel therapeutic candidates for the treatment of malaria.