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Synthesis and biological evaluation of benzenesulphonamide-bearing 1,4,5-trisubstituted-1,2,3-triazoles possessing human carbonic anhydrase I, II, IV, and IX inhibitory activity.
J Enzyme Inhib Med Chem. 2017 Dec; 32(1):1187-1194.JE

Abstract

A library of benzenesulphonamides incorporating 1,2,3-triazole rings functionalised with ester, carboxylic acid, carboxamide, carboxyhydrazide, and hydroxymethyl moieties were synthesised. The carbonic anhydrase (CAs, EC 4.2.1.1) inhibitory activity of the new compounds was assessed against four human (h) isoforms, hCA I, hCA II, hCA IV, and hCA IX. Among them, hCA II and IV are anti-glaucoma drug targets, being involved in aqueous humour secretion within the eye. hCA I was inhibited with Ki's ranging between 8.3 nM and 0.8737 µM. hCA II, the physiologically dominant cytosolic isoform, was excellently inhibited by these compounds, with Ki's in the range of 1.6-9.4 nM, whereas hCA IV was effectively inhibited by most of them, with Ki's in the range of 1.4-55.3 nM. Thirteen of the twenty sulphonamides were found to be excellent inhibitors of tumour associated hCA IX with Ki's ≤ 9.5 nM. Many of the new compounds reported here showed low nM inhibitory action against hCA II, IV, and IX, isoforms involved in glaucoma and some tumours, making them interesting candidates for further medicinal chemistry/pharmacologic studies.

Authors+Show Affiliations

a Department of Chemistry , Kurukshetra University , Kurukshetra , India.a Department of Chemistry , Kurukshetra University , Kurukshetra , India.b Neurofarba Department, Laboratorio di Chimica Bioinorganica, Sezione di Scienze Farmaceutiche , Università degli Studi di Firenze , Firenze , Italy.b Neurofarba Department, Laboratorio di Chimica Bioinorganica, Sezione di Scienze Farmaceutiche , Università degli Studi di Firenze , Firenze , Italy.a Department of Chemistry , Kurukshetra University , Kurukshetra , India.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28891338

Citation

Kumar, Rajiv, et al. "Synthesis and Biological Evaluation of Benzenesulphonamide-bearing 1,4,5-trisubstituted-1,2,3-triazoles Possessing Human Carbonic Anhydrase I, II, IV, and IX Inhibitory Activity." Journal of Enzyme Inhibition and Medicinal Chemistry, vol. 32, no. 1, 2017, pp. 1187-1194.
Kumar R, Sharma V, Bua S, et al. Synthesis and biological evaluation of benzenesulphonamide-bearing 1,4,5-trisubstituted-1,2,3-triazoles possessing human carbonic anhydrase I, II, IV, and IX inhibitory activity. J Enzyme Inhib Med Chem. 2017;32(1):1187-1194.
Kumar, R., Sharma, V., Bua, S., Supuran, C. T., & Sharma, P. K. (2017). Synthesis and biological evaluation of benzenesulphonamide-bearing 1,4,5-trisubstituted-1,2,3-triazoles possessing human carbonic anhydrase I, II, IV, and IX inhibitory activity. Journal of Enzyme Inhibition and Medicinal Chemistry, 32(1), 1187-1194. https://doi.org/10.1080/14756366.2017.1367775
Kumar R, et al. Synthesis and Biological Evaluation of Benzenesulphonamide-bearing 1,4,5-trisubstituted-1,2,3-triazoles Possessing Human Carbonic Anhydrase I, II, IV, and IX Inhibitory Activity. J Enzyme Inhib Med Chem. 2017;32(1):1187-1194. PubMed PMID: 28891338.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synthesis and biological evaluation of benzenesulphonamide-bearing 1,4,5-trisubstituted-1,2,3-triazoles possessing human carbonic anhydrase I, II, IV, and IX inhibitory activity. AU - Kumar,Rajiv, AU - Sharma,Vikas, AU - Bua,Silvia, AU - Supuran,Claudiu T, AU - Sharma,Pawan K, PY - 2017/9/12/entrez PY - 2017/9/12/pubmed PY - 2017/10/11/medline KW - 1,2,3-Triazoles KW - acetazolamide KW - benzenesulphonamide KW - carbonic anhydrase KW - isoforms I, II, IV, IX SP - 1187 EP - 1194 JF - Journal of enzyme inhibition and medicinal chemistry JO - J Enzyme Inhib Med Chem VL - 32 IS - 1 N2 - A library of benzenesulphonamides incorporating 1,2,3-triazole rings functionalised with ester, carboxylic acid, carboxamide, carboxyhydrazide, and hydroxymethyl moieties were synthesised. The carbonic anhydrase (CAs, EC 4.2.1.1) inhibitory activity of the new compounds was assessed against four human (h) isoforms, hCA I, hCA II, hCA IV, and hCA IX. Among them, hCA II and IV are anti-glaucoma drug targets, being involved in aqueous humour secretion within the eye. hCA I was inhibited with Ki's ranging between 8.3 nM and 0.8737 µM. hCA II, the physiologically dominant cytosolic isoform, was excellently inhibited by these compounds, with Ki's in the range of 1.6-9.4 nM, whereas hCA IV was effectively inhibited by most of them, with Ki's in the range of 1.4-55.3 nM. Thirteen of the twenty sulphonamides were found to be excellent inhibitors of tumour associated hCA IX with Ki's ≤ 9.5 nM. Many of the new compounds reported here showed low nM inhibitory action against hCA II, IV, and IX, isoforms involved in glaucoma and some tumours, making them interesting candidates for further medicinal chemistry/pharmacologic studies. SN - 1475-6374 UR - https://www.unboundmedicine.com/medline/citation/28891338/Synthesis_and_biological_evaluation_of_benzenesulphonamide_bearing_145_trisubstituted_123_triazoles_possessing_human_carbonic_anhydrase_I_II_IV_and_IX_inhibitory_activity_ L2 - http://www.tandfonline.com/doi/full/10.1080/14756366.2017.1367775 DB - PRIME DP - Unbound Medicine ER -