Pericosine A as a Marine-Derived Anticancer Agent: Molecular Targets, Bioactivity and Therapeutic Potential Through EGFR and Topoisomerase II Inhibition

Marine-derived natural products have emerged as a rich source of novel anticancer compounds, often exhibiting unique mechanisms distinct from those of terrestrial origin. Pericosine A, a carbasugar metabolite isolated from Periconia byssoides, possesses a rare hybrid shikimate–polyketide framework, contributing to its structural and biological uniqueness. Despite increasing interest in marine-derived bioactives, the anticancer mechanisms and therapeutic relevance of Pericosine A remain insufficiently characterized. This review comprehensively evaluates the current knowledge on Pericosine A, including its cytotoxic activity in vitro across various human cancer cell lines, in vivo efficacy in murine leukemia models, and structure–activity relationships of natural and synthetic derivatives. Pericosine A demonstrated selective cytotoxicity against breast and glioblastoma cell lines. Mechanistic studies have reported activity toward EGFR tyrosine kinase and human topoisomerase II, indicating potential roles in disrupting oncogenic signaling and DNA topology. In vivo, Pericosine A modestly extended survival in P388 leukemia-bearing mice. Semi-synthetic analogs exhibited variable activity, with some showing reduced potency compared to the natural compound. These findings support further investigation of Pericosine A as a marine-derived anticancer scaffold with multi-target potential and underscore the need for continued preclinical development.