Gisele da Costa Ramos

The search for bioactive compounds for the treatment of several diseases has led to the study of endophytic fungi. Neoplastic diseases are among the most significant health concerns due to their high mortality rate, and there is a dearth of efficacious pharmaceutical agents for the treatment of cancer. Gastric cancer is one of the most aggressive forms of cancer and is among those with the highest mortality rates in Brazil. Accordingly, the objective of this study was to identify compounds with cytotoxic activity from the mangrove-derived endophytic fungus Trichoderma sp. Isolation of the chemical compounds was conducted using chromatographic methods, while structural elucidation was achieved through the application of spectroscopic (NMR and UV) and spectrometric (MS) techniques. The fungus Trichoderma sp. was found to produce five distinct koninginins (A, B, C, E, and J). The organic phases of the extracts and isolated compounds were evaluated for their antimicrobial and cytotoxic potentials, respectively, through microdilution testing and the MTT method. In the cytotoxicity assay, both the AF extract and koninginin A demonstrated favorable outcomes, indicating their potential as promising anticancer therapeutic agents.

Gastric cancer is among the major causes of death from neoplasia leading causes of death worldwide, with high incidence rates and problems related to its treatment. Here, we outline how Geissospermum sericeum exerts antitumor activity on the ACP02 cell line (human gastric adenocarcinoma) and the mechanism of cell death. The ethanol extract and fractions, neutral fraction and alkaloid fraction, were characterized by thin-layer chromatography and HPLC-DAD, yielding an alkaloid (geissoschizoline N4-methylchlorine) identified by NMR. The cytotoxicity activity of the samples (ethanol extract, neutral fraction, alkaloid fraction, and geissoschizoline N4-methylchlorine) in HepG2 and VERO cells was determined by MTT. The ACP02 cell line was used to assess the anticancer potential. Cell death was quantified with the fluorescent dyes Hoechst 33342, propidium iodide, and fluorescein diacetate. The geissoschizoline N4-methylchlorine was evaluated in silico against caspase 3 and 8. In the antitumor evaluation, there was observed a more significant inhibitory effect of the alkaloid fraction (IC50 18.29 µg/mL) and the geissoschizoline N4-methylchlorine (IC₅₀ 12.06 µg/mL). However, geissoschizoline N4-methylchlorine showed lower cytotoxicity in the VERO (CC₅₀ 476.0 µg/mL) and HepG2 (CC₅₀ 503.5 µg/mL) cell lines, with high selectivity against ACP02 cells (SI 39.47 and 41.75, respectively). The alkaloid fraction showed more significant apoptosis and necrosis in 24 h and 48 h, with increased necrosis in higher concentrations and increased exposure time. For the alkaloid, apoptosis and necrosis were concentration- and time-dependent, with a lower necrosis rate. Molecular modeling studies demonstrated that geissoschizoline N4-methylchlorine could occupy the active site of caspases 3 and 8 energetically favorably. The results showed that fractionation contributed to the activity with pronounced selectivity for ACP02 cells, and geissoschizoline N4-methylchlor is a promising candidate for caspase inhibitors of apoptosis in gastric cancer. Thus, this study provides a scientific basis for the biological functions of Geissospermum sericeum, as well as demonstrates the potential of the geissoschizoline N4-methylchlorine in the treatment of gastric cancer.

The present work reports the isolation and biological evaluation of three dimeric xanthones from Paecilomyces sp. EJC01.1 isolated as endophytic from Schnella splendens, a typical plant of the Amazon. The compounds phomoxanthone A (1), phomoxanthone B (2) and dicerandrol B (3) were isolated by chromatographic procedures and identified by spectroscopic methods of 1D and 2D NMR and MS. The extracts and compound 1 showed antimicrobial activities against Bacillus subtilis, Escherichia coli, Staphylococcus aureus, Salmonella typhimurium and Pseudomonas aeruginosa. The compound phomoxanthone A (1) showed greater inhibitory activity against B. subtilis (MIC of 7.81 µg mL⁻¹); in addition, it also pronounced inhibitory effect against promastigote forms of Leishmania amazonensis (IC₅₀ of 16.38 ± 1.079 µg mL⁻¹) and epimastigote forms Trypanosoma cruzi (IC₅₀ of 28.61 ± 1.071 µg mL⁻¹). To provide more information about the antibacterial activity of compound 1, an unprecedented molecular docking study was performed using S-ribosyl-homocysteine lyase (LuxS) (PDB ID 2FQO), which showed a possible interaction of phomoxanthone A with two of the residues (His58 and Cys126) that are fundamental for the catalysis mechanism in B. subtilis, which may be associated with the higher activity, when compared to other bacteria, observed in experimental studies. Additionally, quantum studies (DFT) were performed, for which a low gap value (5.982 eV) was observed, which corroborates the reactivity of phomoxanthone A. Thus, phomoxanthone A can be a good agent against pathogenic bacteria.