Betulinic Acid and Brosimine B Hybrid Derivatives as Potential Agents against Female Cancers

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...

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Bibliographic Details
Published in:	Anti-cancer agents in medicinal chemistry Vol. 20; no. 5; p. 622
Main Authors:	Garcês de Couto, Nádia M, Willig, Júlia B, Ruaro, Thaís C, de Oliveira, Diogo Losch, Buffon, Andréia, Pilger, Diogo A, Arruda, Mara S P, Miron, Diogo, Zimmer, Aline R, Gnoatto, Simone C B
Format:	Journal Article
Language:	English
Published:	Netherlands 01-01-2020
Subjects:	Antineoplastic Agents, Phytogenic - chemical synthesis Antineoplastic Agents, Phytogenic - chemistry Antineoplastic Agents, Phytogenic - pharmacology Apoptosis - drug effects Cell Proliferation - drug effects Cell Survival - drug effects Dose-Response Relationship, Drug Drug Screening Assays, Antitumor Female Flavonoids - chemical synthesis Flavonoids - chemistry Flavonoids - pharmacology HeLa Cells Humans Molecular Conformation Moraceae - chemistry Pentacyclic Triterpenes - chemical synthesis Pentacyclic Triterpenes - chemistry Pentacyclic Triterpenes - pharmacology Plants, Medicinal - chemistry Structure-Activity Relationship Tumor Cells, Cultured female cancer triterpene Hybrid compounds anticancer activity flavonoid betulinic acid
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Summary:	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. 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. 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. 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. 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.
ISSN:	1875-5992
DOI:	10.2174/1871520620666200124111634