Mycophenolic Acid Derivatives from Vietnamese Marine Sponge-derived Penicillium sp. 1901NT-2.53.1 Strain and their Antiproliferative Activity

Background: Marine sponges and sponge-associated fungi are rich sources of bioactive compounds with pharmacological potential. However, the secondary metabolites of Vietnamese marine sponge-derived fungi have been poorly studied. Objective: The aim of this study was to investigate the low-molecular-weight compounds in the extract of Penicillium sp. 1901NT-2.53.1 fungus isolated from the Vietnamese marine sponge Cinachyrella sp., and the antiproliferative activity of the isolated compounds. Methods: The structures of isolated compounds were elucidated using spectroscopic methods. The cell viability effects of the compounds were evaluated using MTT assay. Molecular docking was performed using SwissDock. Results: UPLC-MS data suggested the presence of beauvericin, citreorosein, benzopyran and chlorotetracycline derivatives, 2-chloro-1,3,8-trihydroxy-6-(hydroxymethyl)anthracene-9,10- dione and ergosterol peroxide in the fungal extract. Chromatographic separation of the extract resulted in the isolation of three derivatives of mycophenolic acid (MPA), namely penicacids G and K and 4-hydroxy-MPA. Penicacid K was isolated from a natural source for the first time. Penicacid G inhibited the viability of human normal HaCaT keratinocytes with IC50 of 88.3 μM and 72.9 μM for 24 h and 48 h of treatment, respectively. Moreover, penicacid G arrested the proliferation of HaCaT keratinocytes. Both penicacids K and G can interact with the active site of IMPDH2, similar to other derivatives of MPA; however, the differences in their structures are important. Conclusion: Due to the selective action on cancer cells and good druggability, penicacid G may be interesting as an antiproliferative anticancer compound.