2. Academic Validation
  3. New coumarin/sulfocoumarin linked phenylacrylamides as selective transmembrane carbonic anhydrase inhibitors: Synthesis and in-vitro biological evaluation

New coumarin/sulfocoumarin linked phenylacrylamides as selective transmembrane carbonic anhydrase inhibitors: Synthesis and in-vitro biological evaluation

  • Bioorg Med Chem. 2020 Aug 1;28(15):115586. doi: 10.1016/j.bmc.2020.115586.
Baijayantimala Swain 1,  Andrea Angeli 2,  Priti Singh 1,  Claudiu T Supuran 3,  Mohammed Arifuddin 4
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad 500037, India.
  • 2 Università degli Studi di Firenze, Neurofarba Dept., Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, 50019 Sesto, Fiorentino, Florence, Italy.
  • 3 Università degli Studi di Firenze, Neurofarba Dept., Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, 50019 Sesto, Fiorentino, Florence, Italy. Electronic address: [email protected].
  • 4 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad 500037, India; Department of Chemistry, Anwarul Uloom College, 11-3-918, New Malleypally, Hyderabad 500001, T. S., India. Electronic address: [email protected].
PMID: 32631564 DOI: 10.1016/j.bmc.2020.115586
Abstract

Two novel series of phenylacrylamide linked Coumarins and sulfocoumarins (6a-p, 8a-i, and 14a-g) were synthesized and evaluated against four physiologically relevant human carbonic anhydrases (hCAs, EC 4.2.1.1), isoforms hCA I, hCA II, hCA IX and hCA XII for their inhibitory action. All new compounds when screened for Carbonic Anhydrase inhibitory activity have shown selective inhibition towards the tumor associated isoforms hCA IX and XII over CA I and II, with inhibition constants in the submicromolar to low nanomolar range. Compound 6b and 14g exhibited significant inhibition with low nanomolar potency against hCA IX, whereas 6k was effective against hCA XII. Compounds 6b, 14g and 6k may be considered as lead molecules for future development of Cancer therapeutics based on a novel mechanism of action.

Keywords

Carbonic anhydrase; Coumarin; Hypoxia tumor; Phenylacrylamide; Sulfocoumarin; XII isoform; hCA IX.

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