Synthesis of quercetin derivatives as cytotoxic against breast cancer MCF-7 cell line in vitro and in silico studies

Abstract

Background: Quercetin being antioxidant and antiproliferative agent acts by inhibiting CDK2, with an increase in cancer prevalence there is a need to profile quercetin derivatives as CDK2 inhibitors. Materials & method: Schiff bases of quercetin were synthesized as cytotoxic agents against the MCF7 cell line. FTIR, ¹H-NMR and ¹³C-NMR, CHNS/O analysis were employed along with in vivo and in silico activities. Results & conclusion: 2q, 4q, 8q and 9q derivatives have maximum cytotoxic effect with IC₅₀ values 39.7 ± 0.7, 36.65 ± 0.25, 35.49 ± 0.21 and 36.99 ± 0.45, respectively. Molecular docking also confirmed these results 8q has the highest binding potential of -9.165 KJ/mole making it a potent inhibitor of CDK2. These derivatives can be used as lead compounds as potent CDK2 inhibitors.

GRAPHICAL ABSTRACT

Articles highlights

Derivatization

• Quercetin derived Schiff bases were synthesized having better cytotoxic profile against breast cancer cell line.

Characterization

• Spectral analysis confirms the new synthesized compounds.

In vitro studies

• The new derivatives were evaluated CDK-2 inhibitors as potential cytotoxic agent against MCF-7 cell line, 2q, 4q, 8q and 9q derivatives have maximum cytotoxic effect with IC₅₀ values 39.7 ± 0.7, 36.65 ± 0.25, 35.49 ± 0.21 and 36.99 ± 0.45 respectively.

In silico studies

• Molecular docking also confirmed these results 8q has the highest binding potential of -9.165 KJ/mole making it a potent inhibitor of cyclin-dependent kinase 2.

Conclusion

• These derivatives can be used as lead compounds as potent cyclin-dependent kinase 2 inhibitors.

Keywords: :

• Breast cancer and derivatives
• CDK2
• MCF7 cell line
• quercetin

Supplemental material

Supplemental data for this article can be accessed at https://doi.org/10.1080/17568919.2024.2379241

Author contributions

All authors contributed to the study’s conception and design. MR Khan wrote the initial text, reviewed it, carried out the tests, collected the results and handled all other aspects of the study. MA Khan overall supervise all the research process and discussed the concepts, study targets, methods and models. I Ahmad managed the activities. J Ahmed was in charge of maintaining research data as well as coordinating the design and implementation of research activities. H Ahmed verified and reproduced the results and provided study materials and reagents. I Mubeen used statistical tools to analyse the research data. B Awana helped compile the results. F Ullah contributed to programming and software development.

Financial disclosure

The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Data availability statement

Data can be provided on demand from corresponding author.