Sulfonate and sulfamate derivatives possessing benzofuran or benzothiophene nucleus as potent carbonic anhydrase II/IX/XII inhibitors |
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Authors: | Seyed-Omar Zaraei Mohammed I El-Gamal Zainab Shafique Sayyeda Tayyeba Amjad Saifullah Afridi Sumera Zaib Hanan S Anbar Randa El-Gamal Jamshed Iqbal |
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Institution: | 1. Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates;2. Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates;3. Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt;4. Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan;5. Department of Biological Sciences (DBS), National University of Medical Sciences (NUMS), Secretariat c/o Military Hospital, Adjacent to Armed Force Institute of Cardiology, The Mall Rawalpindi 46000, Pakistan;6. Department of Medical Biochemistry, Faculty of Medicine, University of Mansoura, Mansoura 35516, Egypt |
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Abstract: | In the current work, we report the discovery of new sulfonate and sulfamate derivatives of benzofuran- and benzothiophene as potent inhibitors of human carbonic anhydrases (hCAs) II, IX and XII. A set of derivatives, 1a–t, having different substituents on the fused benzofuran and benzothiophene rings (R = alkyl, cyclohexyl, aryl, NH2, NHMe, or NMe2) was designed and synthesized. Most of the derivatives exhibited higher potency than acetazolamide as inhibitors of the purified hCAII, IX and XII isoforms. The most potent inhibitors for hCAII, hCAIX and hCAXII were 1g, 1b and 1d with an IC50 ± SEM values of 0.14 ± 0.03, 0.13 ± 0.03 and 0.17 ± 0.06 µM, respectively. In addition, compounds 1d and 1n exerted preferential inhibitory effect against hCAXII isozyme with good potencies. Some selected compounds were docked within the active pocket of these isozymes and binding of the molecules revealed that sulfonate and sulfamate rings were located towards the active cavity and compounds coordinated to zinc ions. |
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Keywords: | Corresponding authors at: Department of Medicinal Chemistry College of Pharmacy University of Sharjah Sharjah 27272 United Arab Emirates (M I El-Gamal) Benzofuran Benzothiophene Carbonic anhydrase Isoform-selective inhibitors Sulfonate Sulfamate |
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