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Synthesis and biological evaluation of sulfamate derivatives as inhibitors of carbonic anhydrases II and IX

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Abstract

Inhibition of carbonic anhydrases is a potential avenue for treatment of various pathological conditions such as cancer, glaucoma, epileptic seizures, obesity, and altitude sickness. In this study, a series of 4-benzamidophenyl sulfamate derivatives were synthesized and tested against two carbonic anhydrase isoforms namely, carbonic anhydrase II (CA II) and carbonic anhydrase IX (CA IX). All the synthesized compounds inhibited the activity of both isoforms CA II and CA IX at micromolar IC50 concentrations. Compound 1n was found to be the most potent against CA II with an IC50 value of 0.78 μM, whereas compound 1f was the most potent inhibitor against CA IX with an IC50 value of 0.34 μM. Molecular modeling studies of the most potent compounds revealed a network of interactions with important amino acids residues in the active sites of CA II and CA IX.

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Acknowledgements

Authors acknowledge University of Sharjah, United Arab Emirates, for financially supporting this project (grant No. 2201110159 & Drug Design and Discovery Research Group operational fund). The authors gratefully acknowledge the financial support for this research provided by the Higher Education Commission of Pakistan (HEC) via NRPU project No. 20-15846/NRPU/R&D/HEC/2021, German-Pakistani Research Collaboration Programme and Equipment Grant funded by DAAD, Germany.

Funding

This study was funded by University of Sharjah, United Arab Emirates (grant No. 2201110159 & Drug Design and Discovery Research Group operational fund). The authors gratefully acknowledge the financial support for this research provided by the Higher Education Commission of Pakistan (HEC) via NRPU project No. 20-15846/NRPU/R&D/HEC/2021, German-Pakistani Research Collaboration Programme and Equipment Grant funded by DAAD, Germany.

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Authors and Affiliations

  1. Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, 22060, Pakistan

    Saquib Jalil, Saif Ullah & Jamshed Iqbal

  2. Sharjah Institute for Medical Research, University of Sharjah, Sharjah, 27272, United Arab Emirates

    Seyed-Omar Zaraei, Rawan M. Sbenati, Afnan I. Shahin, Bilal O. AlKubaisi, Taleb H. Al-Tel & Mohammed I. El-Gamal

  3. Centre de Recherche du CHU de Québec -, Université Laval, QC, G1V 4G2, Québec, Canada

    Julie Pelletier & Jean Sévigny

  4. Département de microbiologie-infectiologie et d’immunologie, Faculté de Médecine, Université Laval, Québec, QC, G1V 0A6, Canada

    Jean Sévigny

  5. Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates

    Taleb H. Al-Tel & Mohammed I. El-Gamal

  6. Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt

    Mohammed I. El-Gamal

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  1. Saquib Jalil
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Correspondence to Jamshed Iqbal or Mohammed I. El-Gamal.

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Jalil, S., Ullah, S., Zaraei, SO. et al. Synthesis and biological evaluation of sulfamate derivatives as inhibitors of carbonic anhydrases II and IX. Med Chem Res 32, 869–883 (2023). https://doi.org/10.1007/s00044-023-03043-9

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