Synthesis and Antiproliferative Activity of Novel Dehydroabietic Acid-Chalcone Hybrids

Dehydroabietic Acid (DHA, ) 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 derivative...

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Published in:Molecules (Basel, Switzerland) Switzerland), 2022-06, Vol.27 (11), p.3623
Main Authors: Grigoropoulou, Sophia, Manou, Dimitra, Antoniou, Antonia I, Tsirogianni, Artemis, Siciliano, Carlo, Theocharis, Achilleas D, Athanassopoulos, Constantinos M
Format: Article
Language:English
Subjects:
5-FU
Abietanes
Aldehydes
Antineoplastic Agents - pharmacology
Antiproliferatives
Breast cancer
Breast Neoplasms - drug therapy
Cell Line, Tumor
Cell Proliferation
Chalcone - pharmacology
chalcones
Chalcones - pharmacology
Cytotoxicity
Dehydroabietic acid
Drug development
Drug Screening Assays, Antitumor
Estrogens
Estrogens - pharmacology
Female
Fibroblasts
Fluorouracil - pharmacology
Humans
Hybrids
Intermediates
Ketones
Lead compounds
Metastasis
Molecular Structure
Natural products
Phenols
Structure-Activity Relationship
Tumor cell lines
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Summary:Dehydroabietic Acid (DHA, ) 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 ( ) exhibit low micromolar activity levels (IC 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 ( ) and against MDA-MB231 ( and ). Hybrid 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.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules27113623