Synthesis and Antiproliferative Activity of Novel Dehydroabietic Acid-Chalcone Hybrids

Molecules

Dimitra Manou¹  Achilleas D. Theocharis¹  Carlo Siciliano²  Antonia I. Antoniou³  Sophia Grigoropoulou³  Constantinos M. Athanassopoulos³  Artemis Tsirogianni³ 

[1] Biochemistry, Biochemical Analysis & Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, GR-26504 Patras, Greece;Department of Pharmacy, Health and Nutritional Sciences, Edificio Polifunzionale, I-87036 Arcavacata di Rende, CS, Italy;Synthetic Organic Chemistry Laboratory, Department of Chemistry, University of Patras, GR-26504 Patras, Greece;

关键词: dehydroabietic acid;    chalcones;    hybrids;    natural products;    breast cancer;    5-FU;   

DOI  :  10.3390/molecules27113623

来源: DOAJ

【 摘 要 】

Dehydroabietic Acid (DHA, 1) derivatives are known for their antiproliferative properties, among others. In the context of this work, DHA was initially modified to two key intermediates bearing a C18 methyl ester, a phenol moiety at C12, and an acetyl or formyl group at C13 position. These derivatives allowed us to synthesize a series of DHA-chalcone hybrids, suitable for structure–activity relationship studies (SARS), following their condensation with a variety of aryl-aldehydes and methyl ketones. The antiproliferative evaluation of the synthesized DHA-chalcone hybrids against three breast cancer cell lines (the estrogen-dependent MCF-7 and the estrogen-independent MDA-MB-231 and Hs578T) showed that eight derivatives (33, 35, 37, 38, 39, 41, 43, 44) exhibit low micromolar activity levels (IC₅₀ 2.21–11.5 μΜ/MCF-7). For instance, some of them showed better activity compared to the commercial anticancer drug 5-FU against MCF-7 cells (33, 41, 43, 44) and against MDA-MB231 (33 and 41). Hybrid 38 is a promising lead compound for the treatment of MCF-7 breast cancer, exhibiting comparable activity to 5-FU and being 12.9 times less toxic (SI = 22.7). Thus, our findings suggest that DHA-chalcone hybrids are drug candidates worth pursuing for further development in the search for novel breast cancer therapies.

【 授权许可】

Unknown