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Published on: February 9, 2021
Inhibition of Caco-2 and MCF-7 cancer cells using chalcones: synthesis, biological evaluation and computational study
Marco Mellado1, Mauricio Reyna-Jeldes2,3, Caroline Weinstein-Oppenheimer4,5
1Facultad de Ciencias, Instituto de Química, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile.
Abstract:
Cancer is the second death cause worldwide, with breast and colon cancer among the most prevalent types. Traditional treatment strategies have several side effects that inspire the development of novel anticancer agents derived from natural sources, like chalcone derivatives. For this investigation, twenty-three chalcones (4a-w) were synthesized and evaluated as antiproliferative agents against MCF-7 and Caco-2 cells, finding three and two compounds with similar or higher antiproliferative activity than daunorubicin, while only two chalcones showed better selectivity indexes than daunorubicin on MCF-7. From these results, we developed good-performance QSAR models (r > 0.850, q2>0.650), finding several structural features that could modify chalcone activity and selectivity. According to these models, chalcones 4w and 4t have high potency and selectivity against Caco-2 and MCF-7, respectively, which make them attractive candidates for hit-to-lead development of ROS-independent pro apoptotic agents.
Insights
Researchers synthesized novel chalcone derivatives as potential anticancer agents. Chalcones 4w and 4t show high potency and selectivity against colon (Caco-2) and breast (MCF-7) cancer cells, respectively, indicating promise for future drug development.
Area of Science:
- Medicinal Chemistry
- Organic Synthesis
- Cancer Research
Background:
- Cancer is a leading global cause of death, necessitating the development of novel therapeutics.
- Existing cancer treatments often have severe side effects, driving research into natural product-derived agents.
- Chalcone derivatives represent a promising class of natural compounds with potential anticancer properties.
Purpose of the Study:
- To synthesize and evaluate a series of chalcone derivatives for antiproliferative activity against breast (MCF-7) and colon (Caco-2) cancer cell lines.
- To identify structural features influencing the anticancer activity and selectivity of chalcones using Quantitative Structure-Activity Relationship (QSAR) models.
- To identify lead compounds for further development as novel anticancer agents.
Main Methods:
- Synthesis of twenty-three chalcone derivatives (compounds 4a-w).
- In vitro antiproliferative assay against MCF-7 and Caco-2 cancer cell lines.
- Development and validation of Quantitative Structure-Activity Relationship (QSAR) models to correlate structure with activity and selectivity.
Main Results:
- Three chalcones exhibited antiproliferative activity comparable to or exceeding that of daunorubicin against MCF-7 cells.
- Two chalcones demonstrated superior selectivity indexes compared to daunorubicin against MCF-7 cells.
- QSAR models with high performance (r > 0.850, q2 > 0.650) identified key structural determinants of activity and selectivity.
Conclusions:
- Chalcones 4w and 4t possess high potency and selectivity against Caco-2 and MCF-7 cells, respectively.
- These compounds are promising candidates for hit-to-lead optimization in the development of novel pro-apoptotic anticancer agents.
- The identified structural features can guide the design of more effective and selective chalcone-based cancer therapeutics.
