Cytotoxicity and Chemotherapeutic Potential of Natural Rosin Abietane Diterpenoids and their Synthetic Derivatives

Title:Cytotoxicity and Chemotherapeutic Potential of Natural Rosin Abietane Diterpenoids and their Synthetic Derivatives

Volume: 24 Issue: 36

Author(s): Célia Faustino*, Íris Neto, Pedro Fonte and Ana Macedo*

Affiliation:

• iMed.ULisboa - Research Institute for Medicines, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa,Portugal

• CBIOS - Research Centre for Biosciences & Health Technologies, Universidade Lusofona de Humanidades e Tecnologias, Campo Grande 376, 1749-024 Lisboa,Portugal

Keywords: Rosin, abietic acid, dehydroabietic acid, dehydroabietylamine, cytotoxicity, cancer, diterpenes, natural products.

Abstract: Cancer is a major cause of morbidity and mortality worldwide. Chemotherapeutic agents currently used in cancer treatment are associated with severe side effects and development of resistance. Thus, there is a pressing need for novel and more potent anticancer drugs with high selectivity for tumor cells and reduced toxicity to normal tissue. Natural products remain an important source of bioactive compounds and drug prototypes that can lead to new and more effective antitumor agents. Coniferous plants are rich in abietane diterpenoids with a wide range of biological activities that provide useful templates for synthetic modification. Abietic acid and dehydroabietic acid (DHA), the major diterpenic resin acids from Pinus rosin, and dehydroabietylamine found in commercial disproportionated rosin amine, display antibacterial and antitumor properties. These compounds and their synthetic derivatives have been reported as promising anticancer agents with potent growth inhibitory activity against several types of human cancer cell lines, including breast, ovarian, prostate, colon, liver, lung and cervical carcinoma cells. Their mechanisms of action are diverse and include DNA binding, induction of apoptosis or oncosis, tubulin polymerization inhibition and disruption of intracellular cholesterol transport. This review covers the main aspects of natural rosin abietane diterpenoids (abietic acid, DHA and DHAA) and synthetic derivatives concerning their anti-proliferative, cytotoxic and antitumor activities, mechanisms of action and structure- activity relationships relevant for the development of novel anticancer agents for cancer chemotherapy.

Cite this article as:

Faustino Célia *, Neto Íris , Fonte Pedro and Macedo Ana *, Cytotoxicity and Chemotherapeutic Potential of Natural Rosin Abietane Diterpenoids and their Synthetic Derivatives, Current Pharmaceutical Design 2018; 24 (36) . https://dx.doi.org/10.2174/1381612825666190112162817