Chemical Constituents of Taxodium mucronatum (Cupressaceae) and Some of Its Endophytic Fungi, and Their In Silico and In Vitro Evaluations as SARS-CoV-2 Inhibitors and as Cytotoxic Agents.

Considering the importance of the relationships between plants and their fungi, the purpose of this research was to characterize the chemical constituents and bioactivity of Taxodium mucronatum (a tree used in Mexican traditional medicine) and its fungal endophytes. Conventional biotechnological procedures allowed the identification of 17 fungal species, and chemical analysis permitted the isolation of plant and fungal metabolites, characterizing 20 compounds. The inhibition of the SARS-CoV-2 spike protein:ACE2 complex was evaluated using a Ray Biotech kit, and the cytotoxicity against selected tumor cell lines was evaluated by use of the sulforhodamine B assay. The chemical analysis of T. mucronatum afforded diterpenes (1-6), cycloartanes (7--10, not previously reported for this species), and sterols (11, 12). Complementing that analysis, endophytic fungi were identified, mainly from the genus Penicillium, and compounds 13-20 were isolated from some of the fungal cultures. The PASS calculations predicted antiviral activity for compounds 5, 8, 10, and 12, and cytotoxic activity for almost all the isolated compounds. The in vitro results indicate that T. mucronatum and some of its endophytic fungi constitute new sources of bioactive substances that inhibit the formation of the SARS-CoV-2 spike protein:ACE2 complex (such as taxodione, 3) and inhibitors of certain cancer cell lines (5, 13, and 17).