Synthesis, In Silico Evaluation, and Biological Activity Assessment of Chalcone Derivatives Against MCF-7 Cells
Keywords:
Anticancer, Antibacterial, Chalcone, Claisen-Schmidt, MCF-7, Molecular dockingAbstract
Chalcones, characterized by their distinct α,β-unsaturated carbonyl system, exhibit diverse therapeutic properties, including antimicrobial and anticancer activities. The current study focused on synthesizing novel chalcone derivatives using a base-catalyzed Claisen–Schmidt condensation reaction involving substituted benzaldehydes and acetophenone derivatives. These synthesized compounds were structurally verified using FTIR, ¹H NMR, and ¹³C NMR spectroscopy, confirming the successful formation of chalcones via characteristic carbonyl and olefinic peaks. Biological evaluation included cytotoxic assays against the MCF-7 breast cancer cell line, using the MTT assay, where derivative 1C displayed significant cytotoxicity (approximately 10.93% cell viability at 320 ppm), markedly surpassing derivative 1A. Furthermore, antibacterial activities assessed through the agar diffusion method demonstrated pronounced inhibitory effects against Bacillus subtilis, Escherichia coli, and Streptococcus pneumoniae, with compound 1A exhibiting superior antibacterial activity. Additionally, molecular docking studies revealed that derivative 1C showed promising binding affinity (-7.69 kcal/mol) and favorable interactions with key amino acid residues within the estrogen receptor (PDB ID: 5T92), highlighting its potential mechanism of action. These findings emphasize the critical influence of structural variations on biological outcomes and suggest that further optimization of chalcone derivatives with different substitution patterns could yield potent, multifunctional therapeutic agents.
References
M. S. Sultan, "Challenges of breast cancer treatment through microbial therapeutic delivery," Microbial Bioactives, vol. 6, no. 1, pp. 1-15, 2023.
A. K. Nanayakkara, H. W. Boucher, V. G. Fowler Jr, A. Jezek, K. Outterson, and D. E. Greenberg, "Antibiotic resistance in the patient with cancer: Escalating challenges and paths forward," CA: a cancer journal for clinicians, vol. 71, no. 6, pp. 488-504, 2021.
V. B. Kilari and T. Oroszi, "The Misuse of Antibiotics and the Rise of Bacterial Resistance: A Global Concern," Pharmacology & Pharmacy, vol. 15, no. 12, pp. 508-523, 2024.
Z. H. Ali, D. Saleem, A. K. Abbas, B. S. Rasool, and M. S. Cheyad, "Synthesis and estimation of the insecticide and antibacterial activities for some new amide derivatives," Indonesian Journal of Chemistry, vol. 23, no. 6, pp. 1535-1541, 2023.
D. Ni, Y. Li, Y. Qiu, J. Pu, S. Lu, and J. Zhang, "Combining allosteric and orthosteric drugs to overcome drug resistance," Trends in pharmacological sciences, vol. 41, no. 5, pp. 336-348, 2020.
A. A. Jawad, N. R. Jber, B. S. Rasool, and A. K. Abbas, "Tetrazole derivatives and role of tetrazole in medicinal chemistry: An article review," Al-Nahrain Journal of Science, vol. 26, no. 1, pp. 1-7, 2023.
O. Obidiro, G. Battogtokh, and E. O. Akala, "Triple negative breast cancer treatment options and limitations: future outlook," Pharmaceutics, vol. 15, no. 7, p. 1796, 2023.
R. Chaudhari, V. Patel, and A. Kumar, "Cutting-edge approaches for targeted drug delivery in breast cancer: beyond conventional therapies," Nanoscale Advances, 2024.
N. A. Alshaye et al., "Synthesis, DFT, and in silico biological evaluation of chalcone bearing pyrazoline ring against Helicobacter pylori receptors," Heliyon, vol. 10, no. 14, 2024.
R. K. Hebasur, V. V. Koppal, D. A. Yaraguppi, N. B. Gummagol, R. Kusanur, and N. R. Patil, "Comprehensive Analysis of a Chalcone Derivative as an Anticancer Agent: Structural, Spectroscopic, DFT-Based Computational, Electrochemical, and Pharmacological Investigations," 2025.
L. Siddiqui, M. B. Hawsawi, G. A. Chotana, and R. S. Z. Saleem, "Bis-Chalcones: Recent Reports of Their Diverse Applications in Biological and Material Sciences," ACS omega, vol. 9, no. 41, pp. 42061-42090, 2024.
S. K. Mittapalli et al., "Synthesis, Characterization and Evaluation of Antimicrobial and Antioxidant Activities of Novel Chalcone Scaffolds," Letters in Drug Design & Discovery, vol. 21, no. 19, pp. 4792-4812, 2024.
T. T. Mohammed, A. H. Obaid, G. F. Hammeed, and A. K. Abbas, "Modification of Sulfadiazine Antibacterial to Promising Anticancer Schiff Base Derivatives: Synthesis and in Vitro Studies," The International Science of Health Journal, vol. 2, no. 3, pp. 01-10, 2024.
A. A. Jawad et al., "Local chemical compounds: synthesis and characterization with antibiotic application," 2024.
A. N. Mahmood, T. T. Mohammed, R. N. Abdulridha, A. H. Obaid, and A. K. Abbas, "Modification of Amoxicillin drug antibacterial to promising anti-breast cancer MCF-7 imine derivatives: Synthesis and in vitro studies," IAR Journal of Medical Sciences, vol. 5, pp. 1-6, 2024.
H. Karaca and S. Kazancı, "The metal sensing applications of chalcones: The synthesis, characterization and theoretical calculations," Journal of Molecular Structure, vol. 1248, p. 131454, 2022.
J. da Cunha Xavier et al., "Spectroscopic analysis by NMR, FT-Raman, ATR-FTIR, and UV-Vis, evaluation of antimicrobial activity, and in silico studies of chalcones derived from 2-hydroxyacetophenone," Journal of Molecular Structure, vol. 1241, p. 130647, 2021.
M. C. Romeu et al., "Synthesis, crystal structure, ATR-FTIR, FT-Raman and UV spectra, structural and spectroscopic analysis of (3E)‐4‐[4‐(dimethylamine) phenyl] but‐3‐en‐2‐one," Journal of Molecular Structure, vol. 1264, p. 133222, 2022.
L. W. Wijayanti, R. T. Swasono, W. Lee, and J. Jumina, "Synthesis and evaluation of chalcone derivatives as novel sunscreen agent," Molecules, vol. 26, no. 9, p. 2698, 2021.
A. Wilhelm et al., "Synthesis, characterization and cytotoxic evaluation of chalcone derivatives," Journal of Molecular Structure, vol. 1251, p. 132001, 2022.
E. N. Okolo et al., "New chalcone derivatives as potential antimicrobial and antioxidant agent," Scientific reports, vol. 11, no. 1, p. 21781, 2021.
R. Rajasagaran et al., "Structural and Optical Characterization of Anthracene and Bis-Anthracene Chalcone Derivatives as Photosensitizers for Dye-Sensitized Solar Cells," Journal of Molecular Structure, p. 142694, 2025.
B. Ngameni et al., "Design, synthesis, characterization, and anticancer activity of a novel series of O-substituted chalcone derivatives," Bioorganic & Medicinal Chemistry Letters, vol. 35, p. 127827, 2021.
H. Şenol, M. Ghaffari-Moghaddam, G. Ö. A. Toraman, and U. Güller, "Novel chalcone derivatives of ursolic acid as acetylcholinesterase inhibitors: Synthesis, characterization, biological activity, ADME prediction, molecular docking and molecular dynamics studies," Journal of Molecular Structure, vol. 1295, p. 136804, 2024.
M. G. Balamon, E. A. El‐Bordany, N. F. Mahmoud, A. A. Hamed, and A. E. Swilem, "Exploring the Antioxidant Potency of New Naphthalene‐Based Chalcone Derivatives: Design, Synthesis, Antioxidant Evaluation, Docking Study, DFT Calculations," Chemistry & Biodiversity, vol. 20, no. 12, p. e202301344, 2023.
S. Priya, M. M. Islam, S. Kasana, B. D. Kurmi, G. D. Gupta, and P. Patel, "Therapeutic potential of chalcone-1, 2, 3-triazole hybrids as anti-tumour agents: a systematic review and SAR studies," Future Medicinal Chemistry, pp. 1-17, 2025.
T. A. Santos et al., "Methoxy chalcone derivatives: promising antimicrobial agents against Phytopathogens," Chemistry & Biodiversity, vol. 21, no. 11, p. e202400945, 2024.
H. Mirzaei and S. Emami, "Recent advances of cytotoxic chalconoids targeting tubulin polymerization: Synthesis and biological activity," European journal of medicinal chemistry, vol. 121, pp. 610-639, 2016.
M. Zhu et al., "Design, synthesis, and evaluation of chalcone analogues incorporate α, β-Unsaturated ketone functionality as anti-lung cancer agents via evoking ROS to induce pyroptosis," European Journal of Medicinal Chemistry, vol. 157, pp. 1395-1405, 2018.
H. Shi, Y. Zhou, E. Jia, M. Pan, Y. Bai, and Q. Ge, "Bias in RNA‐seq library preparation: current challenges and solutions," BioMed research international, vol. 2021, no. 1, p. 6647597, 2021.
V. H. Masand et al., "Estrogen receptor alpha binders for hormone-dependent forms of breast cancer: e-QSAR and molecular docking supported by X-ray resolved structures," ACS omega, vol. 9, no. 14, pp. 16759-16774, 2024.
N. Kumar et al., "Most recent strategies targeting estrogen receptor alpha for the treatment of breast cancer," Molecular Diversity, vol. 25, pp. 603-624, 2021.
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