Exploration of 3‐aryl pyrazole‐tethered sulfamoyl carboxamides as carbonic anhydrase inhibitors

Author:

Ommi Ojaswitha1,Paoletti Niccolò23,Bonardi Alessandro23,Gratteri Paola3,Bhalerao Harshada Anil4,Sau Shashikanta5,Nanduri Srinivas1ORCID,Mohammed Arifuddin6ORCID,Kalia Nitin Pal5,Sonti Rajesh4,Supuran Claudiu T.23,Yaddanapudi Venkata Madhavi1ORCID

Affiliation:

1. Department of Chemical Sciences National Institute of Pharmaceutical Education and Research (NIPER), Balanagar Hyderabad Telangana India

2. Department NEUROFARBA, Pharmaceutical and Nutraceutical Section University of Florence Sesto Fiorentino (Florence) Italy

3. Laboratory of Molecular Modeling Cheminformatics & QSAR, Department NEUROFARBA, Pharmaceutical and Nutraceutical Section University of Florence Sesto Fiorentino (Florence) Italy

4. Department of Pharmaceutical Analysis National Institute of Pharmaceutical Education and Research (NIPER), Balanagar Hyderabad Telangana India

5. Department of Biological Sciences National Institute of Pharmaceutical Education and Research (NIPER), Balanagar Hyderabad Telangana India

6. Department of Chemistry, Directorate of Distance Education Maulana Azad National Urdu University Hyderabad India

Abstract

AbstractHerein, we report the design and synthesis of two series of pyrazole‐tethered sulfamoyl phenyl acetamides and pyrazole‐tethered sulfamoyl phenyl benzamides. The synthesized compounds were investigated for inhibiting two human carbonic anhydrases, human carbonic anhydrases (hCA) I and II, and those of the bacterial pathogen Mycobacterium tuberculosis, mtCA 1–3. The results indicate that, among the synthesized compounds, pyrazoles with 4‐aminobenzene sulfonamide were more selective toward hCA I and II over mtCAs, and compounds with 3‐aminobenzene sulfonamide were selective toward mtCA 1–3 over hCA I, II. Compound 6g showed significant and selective inhibition toward hCA I and II, with Ki values of 0.0366 and 0.0310 µM, respectively. Compound 5g exhibited the best inhibition toward mtCA 2, with a Ki value of 0.0617 µM. Among the benzamides, compound 9b exhibited significant activity toward mtCA 2, with a Ki value of 0.0696 µM. Selectivity of these compounds was further supported by docking studies. When tested for antitubercular activity, many compounds showed moderate to good inhibition against the Mtb H37Rv strain, with minimum inhibitory concentration (MIC) values in the range of 4–128 µg/mL.

Funder

Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, India

Publisher

Wiley

Subject

Drug Discovery,Pharmaceutical Science

Reference51 articles.

1. World Health Organization.2022.https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2022

2. The β-Carbonic Anhydrases from Mycobacterium tuberculosis as Drug Targets

3. Bacterial Carbonic Anhydrases as Drug Targets: Toward Novel Antibiotics?

4. C. T.Supuran A.Scozzafava Conway2004

5. Structure and function of carbonic anhydrases

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