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Synthesis of novel 4-functionalized 1,5-diaryl-1,2,3-triazoles containing benzenesulfonamide moiety as carbonic anhydrase I, II, IV and IX inhibitors.
Eur J Med Chem. 2018 Apr 25; 150:678-686.EJ

Abstract

The design, synthesis and biological evaluation of a library of 1,2,3-triazole carboxylates incorporating carboxylic acid, hydroxymethyl, carboxylic acid hydrazide, carboxamide and benzenesulfonamide moieties is disclosed. All the novel compounds were investigated for their inhibition potential against carbonic anhydrase (CA, EC 4.2.1.1) human (h) isoforms hCA I, II, IV and IX, well established drug targets. The cytosolic isoform hCA I was inhibited with Ki's ranging between 53.2 nM and 7.616 μM whereas the glaucoma associated cytosolic isoform hCA II was inhibited with Ki's in the range 21.8 nM-0.807 μM. The membrane bound isoform hCA IV, involved in glaucoma and retinitis pigmentosa among others, was effectively inhibited by some of these compounds with Ki < 60 nM, better than the reference drug acetazolamide (AAZ). The tumor associated isoform hCA IX, a recently validated antitumor/antimetastatic drug target, was also effectively inhibited by some of the new sulfonamides, which possess thus the potential to be used as tools for exploring in more details the selective inhibition of hCAs involved in various pathologies.

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Authors+Show Affiliations

Vats L
Department of Chemistry, Kurukshetra University, Kurukshetra, Haryana, 136119, India.
Sharma V
Department of Chemistry, Kurukshetra University, Kurukshetra, Haryana, 136119, India.
Angeli A
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.
Kumar R
Department of Chemistry, Kurukshetra University, Kurukshetra, Haryana, 136119, India.
Supuran CT
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.
Sharma PK
Department of Chemistry, Kurukshetra University, Kurukshetra, Haryana, 136119, India. Electronic address: pksharma@kuk.ac.in.

MeSH

Antigens, NeoplasmCarbonic Anhydrase ICarbonic Anhydrase IICarbonic Anhydrase IXCarbonic Anhydrase InhibitorsDose-Response Relationship, DrugHumansMolecular StructureStructure-Activity RelationshipSulfonamidesTriazoles

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29571155

Citation

Vats, Lalit, et al. "Synthesis of Novel 4-functionalized 1,5-diaryl-1,2,3-triazoles Containing Benzenesulfonamide Moiety as Carbonic Anhydrase I, II, IV and IX Inhibitors." European Journal of Medicinal Chemistry, vol. 150, 2018, pp. 678-686.
Vats L, Sharma V, Angeli A, et al. Synthesis of novel 4-functionalized 1,5-diaryl-1,2,3-triazoles containing benzenesulfonamide moiety as carbonic anhydrase I, II, IV and IX inhibitors. Eur J Med Chem. 2018;150:678-686.
Vats, L., Sharma, V., Angeli, A., Kumar, R., Supuran, C. T., & Sharma, P. K. (2018). Synthesis of novel 4-functionalized 1,5-diaryl-1,2,3-triazoles containing benzenesulfonamide moiety as carbonic anhydrase I, II, IV and IX inhibitors. European Journal of Medicinal Chemistry, 150, 678-686. https://doi.org/10.1016/j.ejmech.2018.03.030
Vats L, et al. Synthesis of Novel 4-functionalized 1,5-diaryl-1,2,3-triazoles Containing Benzenesulfonamide Moiety as Carbonic Anhydrase I, II, IV and IX Inhibitors. Eur J Med Chem. 2018 Apr 25;150:678-686. PubMed PMID: 29571155.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synthesis of novel 4-functionalized 1,5-diaryl-1,2,3-triazoles containing benzenesulfonamide moiety as carbonic anhydrase I, II, IV and IX inhibitors. AU - Vats,Lalit, AU - Sharma,Vikas, AU - Angeli,Andrea, AU - Kumar,Rajiv, AU - Supuran,Claudiu T, AU - Sharma,Pawan K, Y1 - 2018/03/14/ PY - 2018/01/17/received PY - 2018/03/09/revised PY - 2018/03/09/accepted PY - 2018/3/24/pubmed PY - 2018/4/27/medline PY - 2018/3/24/entrez KW - 1,2,3-Triazole KW - Benzenesulfonamide KW - Carbonic anhydrase inhibitors KW - Isoforms I, II, IV, IX SP - 678 EP - 686 JF - European journal of medicinal chemistry JO - Eur J Med Chem VL - 150 N2 - The design, synthesis and biological evaluation of a library of 1,2,3-triazole carboxylates incorporating carboxylic acid, hydroxymethyl, carboxylic acid hydrazide, carboxamide and benzenesulfonamide moieties is disclosed. All the novel compounds were investigated for their inhibition potential against carbonic anhydrase (CA, EC 4.2.1.1) human (h) isoforms hCA I, II, IV and IX, well established drug targets. The cytosolic isoform hCA I was inhibited with Ki's ranging between 53.2 nM and 7.616 μM whereas the glaucoma associated cytosolic isoform hCA II was inhibited with Ki's in the range 21.8 nM-0.807 μM. The membrane bound isoform hCA IV, involved in glaucoma and retinitis pigmentosa among others, was effectively inhibited by some of these compounds with Ki < 60 nM, better than the reference drug acetazolamide (AAZ). The tumor associated isoform hCA IX, a recently validated antitumor/antimetastatic drug target, was also effectively inhibited by some of the new sulfonamides, which possess thus the potential to be used as tools for exploring in more details the selective inhibition of hCAs involved in various pathologies. SN - 1768-3254 UR - https://www.unboundmedicine.com/medline/citation/29571155/Synthesis_of_novel_4_functionalized_15_diaryl_123_triazoles_containing_benzenesulfonamide_moiety_as_carbonic_anhydrase_I_II_IV_and_IX_inhibitors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0223-5234(18)30273-3 DB - PRIME DP - Unbound Medicine ER -
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