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Design and synthesis of novel benzenesulfonamide containing 1,2,3-triazoles as potent human carbonic anhydrase isoforms I, II, IV and IX inhibitors.
Eur J Med Chem. 2018 Jul 15; 155:545-551.EJ

Abstract

In a quest to discover new biologically active compounds, a series of twenty novel heterocyclic derivatives substituted at position 5 with -H (7a-7j) or -CF3 (8a-8j), bearing benzenesulfonamide at N-1 position and various aroyl groups at position 4 of the 1,2,3-triazole ring was synthesized and screened for their carbonic anhydrase (CA, EC 4.2.1.1) inhibition potential against four human (h) isoforms hCA I, II, IV and IX. All the compounds (7a-7j and 8a-8j) were synthesized via [3+2] cycloaddition reaction from 4-azidobenzenesulfonamide. Interestingly, compounds 7a-7j were prepared in one pot manner via enaminone intermediate using novel methodology. All the newly synthesized compounds (7a-7j &8a-8j) were found to be excellent inhibitors of edema related isoform hCA I with their inhibition constant (Ki) ranging from 30.1 to 86.8 nM as compared to standard drug acetazolamide (AAZ) with Ki = 250 nM. Further it was found that most of tested compounds were weaker inhibitors of isoform, hCA II although compounds 7b, 7d-7e, 8a, 8d-8f, 8i (mostly with electron withdrawing substituents) have shown better inhibition potential (Ki < 50 nM). Against glaucoma associated hCA IV, compound 7d was found to be better inhibitor (Ki = 52.4 nM) than AAZ (Ki = 74 nM) while against tumor associated hCA IX, all the compounds have shown moderate inhibition potential. Present study have added one more step in exploring the 1,2,3-triazlole moiety in the medicinal field.

Authors+Show Affiliations

Department of Chemistry, Kurukshetra University, Kurukshetra, 136119, India.Department of Chemistry, Kurukshetra University, Kurukshetra, 136119, India.Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm 188, and Neurofarba Department, Sezione di Scienze Farmaceutiche, Via U. Schiff 6, I-50019, Sesto Fiorentino (Firenze), Italy.Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm 188, and Neurofarba Department, Sezione di Scienze Farmaceutiche, Via U. Schiff 6, I-50019, Sesto Fiorentino (Firenze), Italy. Electronic address: claudiu.supuran@unifi.it.Department of Chemistry, Kurukshetra University, Kurukshetra, 136119, India. Electronic address: pksharma@kuk.ac.in.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29909339

Citation

Kumar, Rajiv, et al. "Design and Synthesis of Novel Benzenesulfonamide Containing 1,2,3-triazoles as Potent Human Carbonic Anhydrase Isoforms I, II, IV and IX Inhibitors." European Journal of Medicinal Chemistry, vol. 155, 2018, pp. 545-551.
Kumar R, Vats L, Bua S, et al. Design and synthesis of novel benzenesulfonamide containing 1,2,3-triazoles as potent human carbonic anhydrase isoforms I, II, IV and IX inhibitors. Eur J Med Chem. 2018;155:545-551.
Kumar, R., Vats, L., Bua, S., Supuran, C. T., & Sharma, P. K. (2018). Design and synthesis of novel benzenesulfonamide containing 1,2,3-triazoles as potent human carbonic anhydrase isoforms I, II, IV and IX inhibitors. European Journal of Medicinal Chemistry, 155, 545-551. https://doi.org/10.1016/j.ejmech.2018.06.021
Kumar R, et al. Design and Synthesis of Novel Benzenesulfonamide Containing 1,2,3-triazoles as Potent Human Carbonic Anhydrase Isoforms I, II, IV and IX Inhibitors. Eur J Med Chem. 2018 Jul 15;155:545-551. PubMed PMID: 29909339.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Design and synthesis of novel benzenesulfonamide containing 1,2,3-triazoles as potent human carbonic anhydrase isoforms I, II, IV and IX inhibitors. AU - Kumar,Rajiv, AU - Vats,Lalit, AU - Bua,Silvia, AU - Supuran,Claudiu T, AU - Sharma,Pawan K, Y1 - 2018/06/08/ PY - 2018/02/09/received PY - 2018/06/05/revised PY - 2018/06/07/accepted PY - 2018/6/18/pubmed PY - 2018/8/8/medline PY - 2018/6/18/entrez KW - 1,2,3-Triazoles KW - Acetazolamide KW - Benzenesulfonamide KW - Carbonic anhydrase isoforms I, II, IV, IX KW - Enaminones SP - 545 EP - 551 JF - European journal of medicinal chemistry JO - Eur J Med Chem VL - 155 N2 - In a quest to discover new biologically active compounds, a series of twenty novel heterocyclic derivatives substituted at position 5 with -H (7a-7j) or -CF3 (8a-8j), bearing benzenesulfonamide at N-1 position and various aroyl groups at position 4 of the 1,2,3-triazole ring was synthesized and screened for their carbonic anhydrase (CA, EC 4.2.1.1) inhibition potential against four human (h) isoforms hCA I, II, IV and IX. All the compounds (7a-7j and 8a-8j) were synthesized via [3+2] cycloaddition reaction from 4-azidobenzenesulfonamide. Interestingly, compounds 7a-7j were prepared in one pot manner via enaminone intermediate using novel methodology. All the newly synthesized compounds (7a-7j &8a-8j) were found to be excellent inhibitors of edema related isoform hCA I with their inhibition constant (Ki) ranging from 30.1 to 86.8 nM as compared to standard drug acetazolamide (AAZ) with Ki = 250 nM. Further it was found that most of tested compounds were weaker inhibitors of isoform, hCA II although compounds 7b, 7d-7e, 8a, 8d-8f, 8i (mostly with electron withdrawing substituents) have shown better inhibition potential (Ki < 50 nM). Against glaucoma associated hCA IV, compound 7d was found to be better inhibitor (Ki = 52.4 nM) than AAZ (Ki = 74 nM) while against tumor associated hCA IX, all the compounds have shown moderate inhibition potential. Present study have added one more step in exploring the 1,2,3-triazlole moiety in the medicinal field. SN - 1768-3254 UR - https://www.unboundmedicine.com/medline/citation/29909339/Design_and_synthesis_of_novel_benzenesulfonamide_containing_123_triazoles_as_potent_human_carbonic_anhydrase_isoforms_I_II_IV_and_IX_inhibitors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0223-5234(18)30512-9 DB - PRIME DP - Unbound Medicine ER -