Synthesis of Tamoxifen-Artemisinin and Estrogen-Artemisinin Hybrids Highly Potent Against Breast and Prostate Cancer

Autor: Svetlana B. Tsogoeva, Svetlana Morozkina, Roman P. Bogautdinov, Tony Fröhlich, Oliver Friedrich, Alexander G. Shavva, Christina Mai, Daniel Gilbert
Rok vydání: 2020
Předmět:
Male
medicine.medical_treatment
01 natural sciences
Biochemistry
chemistry.chemical_compound
Prostate cancer
Drug Discovery
estrogen
General Pharmacology
Toxicology and Pharmaceutics
Artemisinin
skin and connective tissue diseases
Full Paper
Molecular Structure
Full Papers
prostate cancer
Artemisinins
PC-3 Cells
MCF-7 Cells
Molecular Medicine
Female
medicine.drug
medicine.drug_class
Dihydroartemisinin
Antineoplastic Agents
Breast Neoplasms
antitumor agents
Structure-Activity Relationship
breast cancer
Breast cancer
medicine
Humans
Cell Proliferation
hybrids
Pharmacology
Dose-Response Relationship
Drug
010405 organic chemistry
Organic Chemistry
Prostatic Neoplasms
Estrogens
medicine.disease
Afimoxifene
In vitro
0104 chemical sciences
010404 medicinal & biomolecular chemistry
Tamoxifen
artemisinin
chemistry
Estrogen
Cancer research
Drug Screening Assays
Antitumor
Zdroj: Chemmedchem
ISSN: 1860-7187
Popis: In the search for new and effective treatments of breast and prostate cancer, a series of hybrid compounds based on tamoxifen, estrogens, and artemisinin were successfully synthesized and analyzed for their in vitro activities against human prostate (PC‐3) and breast cancer (MCF‐7) cell lines. Most of the hybrid compounds exhibit a strong anticancer activity against both cancer cell lines – for example, EC50 (PC‐3) down to 1.07 μM, and EC50 (MCF‐7) down to 2.08 μM – thus showing higher activities than their parent compounds 4‐hydroxytamoxifen (afimoxifene, 7; EC50=75.1 (PC‐3) and 19.3 μM (MCF‐7)), dihydroartemisinin (2; EC50=263.6 (PC‐3) and 49.3 μM (MCF‐7)), and artesunic acid (3; EC50=195.1 (PC‐3) and 32.0 μM (MCF‐7)). The most potent compounds were the estrogen‐artemisinin hybrids 27 and 28 (EC50=1.18 and 1.07 μM, respectively) against prostate cancer, and hybrid 23 (EC50=2.08 μM) against breast cancer. These findings demonstrate the high potential of hybridization of artemisinin and estrogens to further improve their anticancer activities and to produce synergistic effects between linked pharmacophores.
Stronger together: The synthesis and biological investigation of four tamoxifen‐artemisinin and 16 estrogen‐artemisinin hybrid molecules are presented. In most cases, the anticancer activities of these new compounds exceed those of their parent compounds and reference drugs. The developed hybrids exhibit excellent in vitro activity against human prostate (PC‐3) and breast cancer (MCF‐7) cell lines.
Databáze: OpenAIRE
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