Synthesis, Antiproliferative and Antifungal Activities of 1,2,3-Triazole-Substituted Carnosic Acid and Carnosol Derivatives

Molecules

Mariano Walter Pertino³  Cristina Theoduloz²  Estefania Butassi¹  Susana Zacchino¹  Guillermo Schmeda-Hirschmann³ 

[1] Facultad de Ciencias Bioquímicas y Farmacéuticas, Farmacognosia, Universidad Nacional de Rosario, Suipacha 531, Rosario 2000, Argentina; E-Mails:;Facultad de Ciencias de la Salud, Universidad de Talca, Casilla 747, Talca, Chile; E-Mail:;Instituto de Química de Recursos Naturales, Universidad de Talca, Casilla 747, Talca, Chile; E-Mail:

关键词: carnosic acid;    carnosol;    click chemistry;    antiproliferative;    antifungal;   

DOI  :  10.3390/molecules20058666

来源: mdpi

【 摘 要 】

Abietane diterpenes exhibit an array of interesting biological activities, which have generated significant interest among the pharmacological community. Starting from the abietane diterpenes carnosic acid and carnosol, twenty four new triazole derivatives were synthesized using click chemistry. The compounds differ in the length of the linker and the substituent on the triazole moiety. The compounds were assessed as antiproliferative and antifungal agents. The antiproliferative activity was determined on normal lung fibroblasts (MRC-5), gastric epithelial adenocarcinoma (AGS), lung cancer (SK-MES-1) and bladder carcinoma (J82) cells while the antifungal activity was assessed against Candida albicans ATCC 10231 and Cryptococcus neoformans ATCC 32264. The carnosic acid γ-lactone derivatives 1–3 were the most active antiproliferative compounds of the series, with IC₅₀ values in the range of 43.4–46.9 μM and 39.2–48.9 μM for MRC-5 and AGS cells, respectively. Regarding antifungal activity, C. neoformans was the most sensitive fungus, with nine compounds inhibiting more than 50% of its fungal growth at concentrations ≤250 µg∙mL⁻¹. Compound 22, possessing a p-Br-benzyl substituent on the triazole ring, showed the best activity (91% growth inhibition) at 250 µg∙mL⁻¹ In turn, six compounds inhibited 50% C. albicans growth at concentrations lower than 250 µg∙mL⁻¹.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.