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Synthesis, Structure, and In Vitro Pharmacological Evaluation of some New Pyrimidine-2-Sulfonamide Derivatives and Their Molecular Docking Studies on Human Estrogen Receptor Alpha and CDK2/Cyclin Proteins

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Abstract

In this approach, novel pyrimidine-2-sulfonamide derivatives based on the 2H-chromen-2-one moiety were synthesized and evaluated as anticancer and antibacterial agents. Molecular docking studies have been conducted to investigate the interactions of these compounds with human estrogen receptor alpha (ERα) and 4CDK2/Cyclin proteins. The studies have shown that these derivatives can bind to (ERα and 4CDK2/Cyclin) proteins with high affinity, suggesting that they may have potential as anti-cancer agents. The cytotoxicity of these compounds was investigated in vitro against MCF-7 and HCT-116 cancer cell lines, with encouraging results being obtained for some of the tested derivatives. In addition, antibacterial studies revealed that some of the synthesized derivatives exhibited effectiveness against tested microorganisms compared to the well-established antibacterial drug Ciprofloxacin. Further, molecular interaction studies revealed that the synthesized molecules have a significant binding affinity toward human estrogen receptor Alpha and CDK2/cyclin A proteins.

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Fig. 1.
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Scheme 1.

DATA AVAILABILITY

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This research work was funded by Institutional Fund Projects under grant no. IFPIP-301-130-1443. The authors gratefully acknowledge technical and financial support provided by the ministry of Education and King Abdulaziz University, DSR, Jeddah, Saudi Arabia.

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Authors and Affiliations

  1. Department of Chemistry, General Directorate of Education in Babylon, University of Babylon, 5100, Al-Hilla, Iraq

    Qassim A. H. Jaber

  2. Department of Chemistry, College of Sciences for Woman, University of Babylon, 5100, Al-Hilla, Iraq

    Ahmed Hassen Shentaif & Mohammed Almajidi

  3. Department of Pharmaceutical Chemistry, Prof. Ravindra Nikam College of Pharmacy, Gondur, Dhule, 424002, Maharashtra, India

    Iqrar Ahmad

  4. Division of Computer Aided Drug Design, Department of Pharmaceutical Chemistry, R.C. Patel Institute of Pharmaceutical Education and Research, Shirpur, 425405, Maharashtra, India

    Harun Patel

  5. Faculty of Pharmacy, MAHSA University, Bandar Saujana Putra, Jenjarom, 42610, Selangor, Malaysia

    Abul Kalam Azad

  6. Department of Pharmacology and Toxicology, Unaizah College of Pharmacy, Qassim University, 52571, Buraydah, Saudi Arabia

    Sulaiman Mohammed Alnasser

  7. Department of Biological Sciences, University collage of Haqel, University of Tabuk, 71491, Tabuk, Saudi Arabia

    Hanan Ali Alatawi

  8. Departments of Biomedical and Environmental Engineering, California Innovations Corporation, San Diego, 4211, CA, USA

    Farid Menaa

  9. Department of Chemistry, King Abdulaziz University, P.O. Box 80203, 21589, Jeddah, Saudi Arabia

    Sulaiman Y.M. Alfaifi & Mohammed M. Rahman

  10. Cellular and Molecular Imaging Laboratory, Department of Neurosurgery, Henry Ford Hospital, Box 82, Detroit, 2799, MI, USA

    Meser M. Ali

  11. Kimberlite chemicals India Pvt. Ltd, KIADB III Phase, Doddaballapur, Bangalore, 561203, Karnataka, India

    S. J. Aditya Rao

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  1. Qassim A. H. Jaber
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  2. Ahmed Hassen Shentaif
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Contributions

The authors QAJ, AHS, MA, AKA, and SMA—selected the literature data on the review topic. The authors IA, HP, HAA, FM, SYA, AMR, MSA, and ARS—contributed to manuscript preparation.

All authors participated in the discussions.

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Jaber, Q.A.H., Shentaif, A.H., Almajidi, M. et al. Synthesis, Structure, and In Vitro Pharmacological Evaluation of some New Pyrimidine-2-Sulfonamide Derivatives and Their Molecular Docking Studies on Human Estrogen Receptor Alpha and CDK2/Cyclin Proteins. Russ J Bioorg Chem 49 (Suppl 1), S106–S118 (2023). https://doi.org/10.1134/S1068162023080095

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