Bioprospecting of Endolichenic Fungus Phanerochaetechrysosporium from Mangrove Associated Lichen Bactrosporamyriadea for Anticancer Leads

Endolichenic fungi (ELF) are gaining attention as a promising source for novel cytotoxic compounds. In this study, lichens Bactrosporamyriadea and Arthoniaantillarum, collected from the mangroves of Negombo Lagoon in Sri Lanka, were examined to identify their associated ELFs. Phanerochaetechrysosporium, Lasiodiplodiatheobromae, and Xylariafeejeensis were isolated from B. myriadea, while Xylariapsidii, Daldiniaeschscholtzii, and Nodulisporium sp. were obtained from A. antillarum. The ethyl acetate extracts of these ELFs were screened for cytotoxic activity against the MCF-7 cell line, with P. chrysosporium extract showing potent cytotoxicity. The purified compounds from this extract were identified as spirolaxine (1), phanerosporic acid (2), and 5-(14-hydroxypentadecyl)-resorcinol (3). Their structures were determined using Fourier Transform Infrared, Nuclear Magnetic Resonance spectroscopy and Liquid Chromatography-High Resolution mass spectrometry, while their absolute configurations were established through circular dichroism and time-dependent density functional theory calculations. The compounds demonstrated moderate cytotoxic activity against human breast (MCF-7), oral (CAL-27), and lung (A549) cancer cell lines. Compound 1 exhibited the strongest cytotoxicity against oral cancer, with an IC<inf>50</inf> value of 10.62 ± 0.02 µM. Compound 2 was effective against both MCF-7 and A549 cell lines, with IC<inf>50</inf> values of 9.86 ± 0.02 µM and 6.66 ± 0.04 µM, respectively. This is the first report of compound 3 from a natural source, as it was previously documented only as a semi-synthetic derivative of compound 2. The study highlights the potential of the ELF P. chrysosporium to produce cytotoxic secondary metabolites.