Preparation of Sesquiterpene Lactone Derivatives: Cytotoxic Activity and Selectivity of Action

BEER, MARÍA F.; BIVONA, AUGUSTO E.; SÁNCHEZ ALBERTI, ANDRÉS; CERNY, NATACHA; RETA, GUILLERMO F.; MARTÍN, VÍCTOR S.; PADRÓN, JOSÉ M.; MALCHIODI, EMILIO L.; SÜLSEN, VALERIA P.; DONADEL, OSVALDO J.

MOLECULES

MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI

Año: 2019 vol. 24

1420-3049

Cancer is one of the most important causes of death worldwide. Solid tumors representthe great majority of cancers (>90%) and the chemotherapeutic agents used for their treatment arestill characterized by variable efficacy and toxicity. Sesquiterpene lactones are a group of naturallyoccurring compounds that have displayed a diverse range of biological activities including cytotoxicactivity. A series of oxygenated and oxy-nitrogenated derivatives (4?15) from the sesquiterpenelactones cumanin (1), helenalin (2), and hymenin (3) were synthesized. The silylated derivatives ofhelenalin, compounds 13 and 14, were found to be the most active against tumor cell lines, with GI50values ranging from 0.15 to 0.59 M. The ditriazolyl cumanin derivative (11) proved to be moreactive and selective than cumanin in the tested breast, cervix, lung, and colon tumor cell lines.This compound was the least toxic against splenocytes (CC50 = 524.1 M) and exhibited the greatestselectivity on tumor cell lines. This compound showed a GI50 of 2.3 M and a SI of 227.9 on WiDrhuman colon tumor cell lines. Thus, compound 11 can be considered for further studies and is acandidate for the development of new antitumor agents.