Shedding light on Paraconiothyrium brasiliense: Secondary metabolites, biological activities, and computational studies

Abstract

Fungi are renowned as a prolific source for the biosynthesis of therapeutically valuable metabolites. Paraconiothyrium genus (Leptosphaeriaceae) demonstrates remarkable potential for the biosynthesis of a wide array of metabolites, including macrolides, terpenoids, polyketides, phenolics, and furanones, which exhibit diverse bioactivities. The present review focused on the reported metabolites derived from Paraconiothyrium brasiliense, including their chemical structures and bioactive properties. Furthermore, it delves into the elucidation of the biosynthetic pathways for these metabolites. This review encompasses the description of over 92 compounds reported in the literature from 2010 to October 2023. In addition, in silico studies may explain the potential mechanisms underlying the neuroprotective properties of certain furanone derivatives against central nervous system disorders. Among the tested compounds against KEAP1 through Keap1/Nrf2 pathway-mediated neuroprotection, paraconfuranone I (48), paraconfuranone (50), and paraconfuranone L (51) displayed docking scores ranging from −6.158 to −6.612 kcal/mol, similar to the exciting reference compound which achieved the highest docking score of −6.633 kcal/mol. Moreover, new potential activities of some compounds as inhibitors against the LasR target of Pseudomonas aeruginosa were elucidated using molecular docking and absorption, distribution, metabolism, excretion, and toxicity prediction. Specifically, 1-(1’,2’-dideoxy-α-D-nucleopyranosyl)-β-carboline (73) had the highest docking score at −11.327 kcal/mol, followed by 1-acetyl-β-carboline (75) at −10.055 kcal/mol, in comparison to reference compound (docking score −10.023 kcal/ mol). In addition, ten other compounds displayed competitive docking scores ranging from −9.813 to −9.312 kcal/ mol. This suggested the potential of P. brasiliense as a promising lead for antibacterial and neuroprotective agents.