Natural bioresources, predominantly plants, have always been regarded as the richest source of drugs for diseases threatening humanity. Additionally, microorganism-originating metabolites have been extensively explored as weapons against bacterial, fungal, and viral infections. However, the biological potential of metabolites produced by plant endophytes still remains understudied, despite significant efforts reflected in recently published papers. Thus, our goal was to evaluate the metabolites produced by endophytes isolated from Marchantia polymorpha and to study their biological properties, namely anticancer and antiviral potential. The cytotoxicity and anticancer potential were assessed using the microculture tetrazolium technique (MTT) against non-cancerous VERO cells and cancer cells-namely the HeLa, RKO, and FaDu cell lines. The antiviral potential was tested against the human herpesvirus type-1 replicating in VERO cells by observing the influence of the extract on the virus-infected cells and measuring the viral infectious titer and viral load. The most characteristic metabolites identified in the ethyl acetate extract and fractions obtained by use of centrifugal partition chromatography (CPC) were volatile cyclic dipeptides, cyclo(l-phenylalanyl-l-prolyl), cyclo(l-leucyl-l-prolyl), and their stereoisomers. In addition to the diketopiperazine derivatives, this liverwort endophyte also produced arylethylamides and fatty acids amides. The presence of N-phenethylacetamide and oleic acid amide was confirmed. The endophyte extract and isolated fractions showed a potential selective anticancer influence on all tested cancer cell lines. Moreover, the extract and the first separated fraction noticeably diminished the formation of the HHV-1-induced cytopathic effect and reduced the virus infectious titer by 0.61-1.16 log and the viral load by 0.93-1.03 log. Endophytic organisms produced metabolites with potential anticancer and antiviral activity; thus, future studies should aim to isolate pure compounds and evaluate their biological activities.
Keywords: antiviral activity; cytotoxic and anticancer activity; diketopiperazines; liverwort endophytes.