Research Article

Challenging breast cancer through novel sulfonamide–pyridine hybrids: design, synthesis, carbonic anhydrase IX inhibition and induction of apoptosis

Drug Radiation Research, National Center for Radiation Research & Technology (NCRRT), Egyptian Atomic Energy Authority, Cairo, Egypt

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Reham MM Elhazek

Drug Radiation Research, National Center for Radiation Research & Technology (NCRRT), Egyptian Atomic Energy Authority, Cairo, Egypt

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Ahmed E Gouda

Pharmaceutical Research Department, Nawah Scientific, Cairo, Egypt

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Amira Khalil

*Author for correspondence:

E-mail Address: Amira.Khalil@bue.edu.eg

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The British University in Egypt (BUE), El-Sherouk City, Cairo, 11837, Egypt

The Center for Drug Research & Development (CDRD), Faculty of Pharmacy, The British University in Egypt (BUE), El-Sherouk City, Cairo, 11837, Egypt

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Marwa G Elgazzar

Drug Radiation Research, National Center for Radiation Research & Technology (NCRRT), Egyptian Atomic Energy Authority, Cairo, Egypt

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Published Online:10 Feb 2023https://doi.org/10.4155/fmc-2022-0197

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Abstract

Background: Among the important key modulators of the tumor microenvironment and hypoxia is a family of enzymes named carbonic anhydrases. Herein, 11 novel sulfonamide–pyridine hybrids (2–12) were designed, synthesized and biologically evaluated for their potential use in targeting breast cancer. Methods & results: The para chloro derivative 7 reported the highest cytotoxic activity against the three breast cancer cell lines used. In addition, compound 7 was found to induce cell cycle arrest and autophagy as well as delaying wound healing. The IC₅₀ of compound 7 against carbonic anhydrase IX was 253 ± 12 nM using dorzolamide HCl as control. Conclusion: This study encourages us to expand the designed library, where more sulfonamide derivatives would be synthesized and studied for their structure–activity relationships.

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Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Received 13 August 2022

Accepted 1 December 2022

Published online 10 February 2023

Published in print January 2023

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To view the supplementary data that accompany this paper please visit the journal website at: www.future-science.com/doi/suppl/10.4155/fmc-2022-0197

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The authors have no relevant affiliations or 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.

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

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