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

Molecules

Adrián Puerta¹  José M. Padrón¹  Augusto E. Bivona²  Andrés Sánchez Alberti²  Emilio L. Malchiodi²  Osvaldo J. Donadel³  Carlos E. Tonn³  María F. Beer³  Guillermo F. Reta³  Natacha Cerny⁴  Valeria P. Sülsen⁵ 

[1] BioLab, Instituto Universitario de Bio-Orgánica Antonio González (IUBO-AG), Universidad de La Laguna, Avda, Astrofísico Francisco Sánchez 2, 38206 La Laguna, Spain;Cátedra de Inmunología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires 1113, Argentina;INTEQUI-CONICET, Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, San Luis 1445, Argentina;Instituto de Estudios de la Inmunidad Humoral (IDEHU), CONICET–Universidad de Buenos Aires, Buenos Aires 1113, Argentina;Instituto de Química y Metabolismo del Fármaco (IQUIMEFA), CONICET–Universidad de Buenos Aires, Buenos Aires 1113, Argentina;

关键词: sesquiterpenes;    antiproliferative activity;    Asteraceae;    tessaric acid;    ilicic acid;    ilicic alcohol;   

DOI  :  10.3390/molecules27103067

来源: DOAJ

【 摘 要 】

Cancer is one of the most important causes of death worldwide. Solid tumors represent the vast majority of cancers (>90%), and the chemotherapeutic agents used for their treatment are still characterized by variable efficacy and toxicity. Sesquiterpenes are a group of natural compounds that 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, and ilicic alcohol and their semisynthetic derivatives against HeLa, T-47D, WiDr, A549, HBL-100, and SW1573 cell lines were evaluated. The effect of the compounds on Trypanosoma cruzi epimastigotes was also assessed. The selectivity index was calculated using murine splenocytes. Derivatives 13 and 15 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 to improvements in activity compared to those corresponding to the starting natural product (3), with GI₅₀ values ranging between 12 (±1.5) and 17 (±1.1) μM and 16 being the most active compound. In relation to the anti-T. cruzi activity, derivatives 7 and 16 obtained from tessaric acid and ilicic acid were among the most active and selective compounds with IC₅₀ values of 9.3 and 8.8 µM (SI = 8.0 and 9.4), respectively.

【 授权许可】

Unknown