Title:Betulinic Acid and Brosimine B Hybrid Derivatives as Potential Agents against Female Cancers
Volume: 20
Issue: 5
Author(s): Nádia M. Garcês de Couto, Júlia B. Willig, Thaís C. Ruaro, Diogo Losch de Oliveira, Andréia Buffon, Diogo A. Pilger, Mara S.P. Arruda, Diogo Miron, Aline R. Zimmer and Simone C.B. Gnoatto*
Affiliation:
- Post-graduation of Pharmaceutical Science Program, Faculty of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre,Brazil
Keywords:
Hybrid compounds, triterpene, betulinic acid, flavonoid, anticancer activity, female cancer.
Abstract:
Background: Cancer is a multifactorial disease, representing one of the leading causes of death
worldwide. On a global estimate, breast cancer is the most frequently occurring cancer in women and cervical
cancer, the fourth most common. Both types of cancer remain the major cause of cancer-related mortality in
developing countries. A strategy for rational drug design is hybridization, which aims to bring together in one
molecule, two or more pharmacophores in order to reach several biological targets.
Objective: The objective of this work was to develop new hybrids based on natural pharmacophores: Betulinic
acid (1) and brosimine b (2), active in female cancer cell lines.
Methods: The coupling reactions were carried out by Steglich esterification. Different compounds were designed
for the complete and simplified structural hybridization of molecules. The anticancer activities of the
compounds were evaluated in human cervical adenocarcinoma (HeLa), human cervical metastatic epidermoid
carcinoma (ME-180), and human breast adenocarcinoma (MCF-7) cell lines.
Results: Hybrid 3 presented higher potency (IC50 = 9.2 ± 0.5μM) and SI (43.5) selectively in MCF-7 cells (in
relation to Vero cells) with its cytotoxic effect occurring via apoptosis. In addition, compound 6 showed activity
in MCF-7 and HeLa cells with intermediate potency, but with high efficacy, acting via apoptosis as well.
Conclusion: In this context, we showed that the combination of two complex structures generated the development
of hybrids with differing inhibitory profiles and apoptotic modes of action, thus representing potential
alternatives in female cancer treatment.
