Oxonitrogenated Derivatives of Eremophilans and Eudesmans: Antiproliferative and Anti-Trypanosoma cruzi Activity

BEER, MARÍA F.; RETA, GUILLERMO F.; ADRIAN PUERTA; AUGUSTO E. BIVONA; ANDRES SANCHEZ ALBERTI; NATACHA CERNY; MALCHIODI E; CARLOS TONN; JOSE M PADRON; SÜLSEN, VALERIA P.; DONADEL, OSVALDO J.

MOLECULES

MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI

Año: 2022

1420-3049

Cancer is one of the most important causes of death worldwide. Solid tumors representthe vast majority of cancers (>90%), and the chemotherapeutic agents used for their treatment arestill characterized by variable efficacy and toxicity. Sesquiterpenes are a group of natural compoundsthat have shown a wide range of biological activities, including cytotoxic and antiparasitic activity,among others. The antiproliferative activity of natural sesquiterpenes, tessaric acid, ilicic acid, andilicic alcohol and their semisynthetic derivatives against HeLa, T-47D, WiDr, A549, HBL-100, andSW1573 cell lines were evaluated. The effect of the compounds on Trypanosoma cruzi epimastigoteswas also assessed. The selectivity index was calculated using murine splenocytes. Derivatives 13 and15 were the most antiproliferative compounds, with GI50 values ranging between 5.3 (±0.32) and 14(±0.90) μM, in all cell lines tested. The presence of 1,2,3-triazole groups in derivatives 15?19 led toimprovements in activity compared to those corresponding to the starting natural product (3), withGI50 values ranging between 12 (±1.5) and 17 (±1.1) μM and 16 being the most active compound. Inrelation to the anti-T. cruzi activity, derivatives 7 and 16 obtained from tessaric acid and ilicic acidwere among the most active and selective compounds with IC50 values of 9.3 and 8.8 μM (SI = 8.0and 9.4), respectively.