Abstract

Paecilomyces subglobosus CBK3, an endophytic fungus isolated from the traditional medicinal fern Cyathea contaminans (Hook.) Copel. has been recognized for its capacity to produce bioactive secondary metabolites. Chromatographic separation of the dichloromethane fraction of P. subglobosus CBK3 led to the isolation of two major compounds: O-methylcorypaline (OMC, 0.25%) and phenylglyoxylic acid (PGA, 0.02%). Structural elucidation was confirmed using liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. To assess their therapeutic potential, molecular docking simulations were performed against cyclooxygenase-2, angiotensin II receptor type 1 (AT1 ), and angiotensin-converting enzyme (ACE). OMC demonstrated a stronger binding affinity to ACE (−5.54 kcal/mol) compared to the reference drug captopril (−4.92 kcal/mol) and was comparable to the natural ligand (−5.40 kcal/mol). However, its affinity for AT1 was relatively lower (−5.49 kcal/mol). Furthermore, the analysis of absorption, distribution, metabolism, excretion, and toxicity revealed that OMC possesses a more favorable pharmacokinetic profile than PGA. These findings underscore the potential of OMC as a promising lead compound for developing novel antihypertensive agents derived from fungal endophytes.

Key words: O-methylcorypaline; phenylglyoxylic acid; LC-QToF-MS/MS; Molecular docking; Natural product drug discovery