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Continued exploration and tail approach synthesis of benzenesulfonamides containing triazole and dual triazole moieties as carbonic anhydrase I, II, IV and IX inhibitors.
Eur J Med Chem. 2019 Dec 01; 183:111698.EJ

Abstract

A library of twenty two novel 1,2,3-triazole benzenesulfonamides incorporating thiosemicarbazide, 5(4H)-thione-1,2,4-triazole and variously substituted phenacyl appended 1,2,4-triazole as tail were designed, synthesized and assessed for their efficacy as inhibitors against carbonic anhydrase human (h) isoforms hCA I, II, IV and IX. The physiologically important and off-target cytosolic isoform hCA I was weakly inhibited by most of the newly synthesized sulfonamides while the glaucoma associated isoform hCA II was moderately inhibited with KIs spanning in low nanomolar range (KI = 8.0 nM-0.903 μM). The membrane bound isoform hCA IV, which is known to be involved in glaucoma and retinitis pigmentosa among others, was strongly inhibited by all newly synthesized sulfonamides out of which nine compounds inhibited isoform hCA IV even more effectively as compared to standard drug acetazolamide (AAZ). The membrane bound isoform hCA IX, associated with growth of tumor cells, was moderately inhibited with KIs ranging between 51 nM-3.198 μM. The effect of appending variously substituted tails on heterocyclic moieties over inhibition potential of synthesized sulfonamides is also disclosed which can be of further interest in pharmacological studies for exploring synthesis of isoform selective inhibitors.

Authors+Show Affiliations

Department of Chemistry, Kurukshetra University, Kurukshetra, Haryana, 136119, India; Government College Bherian, Pehowa, Kurukshetra, Haryana, 136128, India.Department of Chemistry, Kurukshetra University, Kurukshetra, Haryana, 136119, India; Ch. Mani Ram Godara Government College for Women, Bhodia Khera, Fatehabad, Haryana, 125050, India.NEUROFARBA Department, Pharmaceutical and Nutraceutical Section, University of Firenze, Via U. Schiff 6, 50019, Sesto Fiorentino, Firenze, Italy.NEUROFARBA Department, Pharmaceutical and Nutraceutical Section, Laboratory of Molecular Modeling Cheminformatics & QSAR, University of Firenze, Via U. Schiff 6, 50019, Sesto Fiorentino, Firenze, Italy.NEUROFARBA Department, Pharmaceutical and Nutraceutical Section, Laboratory of Molecular Modeling Cheminformatics & QSAR, University of Firenze, Via U. Schiff 6, 50019, Sesto Fiorentino, Firenze, Italy.NEUROFARBA Department, Pharmaceutical and Nutraceutical Section, University of Firenze, Via U. Schiff 6, 50019, Sesto Fiorentino, Firenze, Italy. Electronic address: claudiu.supuran@unifi.it.Department of Chemistry, Kurukshetra University, Kurukshetra, Haryana, 136119, India. Electronic address: pksharma@kuk.ac.in.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31539777

Citation

Vats, Lalit, et al. "Continued Exploration and Tail Approach Synthesis of Benzenesulfonamides Containing Triazole and Dual Triazole Moieties as Carbonic Anhydrase I, II, IV and IX Inhibitors." European Journal of Medicinal Chemistry, vol. 183, 2019, p. 111698.
Vats L, Kumar R, Bua S, et al. Continued exploration and tail approach synthesis of benzenesulfonamides containing triazole and dual triazole moieties as carbonic anhydrase I, II, IV and IX inhibitors. Eur J Med Chem. 2019;183:111698.
Vats, L., Kumar, R., Bua, S., Nocentini, A., Gratteri, P., Supuran, C. T., & Sharma, P. K. (2019). Continued exploration and tail approach synthesis of benzenesulfonamides containing triazole and dual triazole moieties as carbonic anhydrase I, II, IV and IX inhibitors. European Journal of Medicinal Chemistry, 183, 111698. https://doi.org/10.1016/j.ejmech.2019.111698
Vats L, et al. Continued Exploration and Tail Approach Synthesis of Benzenesulfonamides Containing Triazole and Dual Triazole Moieties as Carbonic Anhydrase I, II, IV and IX Inhibitors. Eur J Med Chem. 2019 Dec 1;183:111698. PubMed PMID: 31539777.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Continued exploration and tail approach synthesis of benzenesulfonamides containing triazole and dual triazole moieties as carbonic anhydrase I, II, IV and IX inhibitors. AU - Vats,Lalit, AU - Kumar,Rajiv, AU - Bua,Silvia, AU - Nocentini,Alessio, AU - Gratteri,Paola, AU - Supuran,Claudiu T, AU - Sharma,Pawan K, Y1 - 2019/09/12/ PY - 2019/06/26/received PY - 2019/09/10/revised PY - 2019/09/11/accepted PY - 2019/9/21/pubmed PY - 2019/9/21/medline PY - 2019/9/21/entrez KW - 1,2,3-Triazole KW - 1,2,4-Triazole KW - Benzenesulfonamide KW - CA isoforms KW - Carbonic anhydrase inhibitors KW - Tail approach synthesis SP - 111698 EP - 111698 JF - European journal of medicinal chemistry JO - Eur J Med Chem VL - 183 N2 - A library of twenty two novel 1,2,3-triazole benzenesulfonamides incorporating thiosemicarbazide, 5(4H)-thione-1,2,4-triazole and variously substituted phenacyl appended 1,2,4-triazole as tail were designed, synthesized and assessed for their efficacy as inhibitors against carbonic anhydrase human (h) isoforms hCA I, II, IV and IX. The physiologically important and off-target cytosolic isoform hCA I was weakly inhibited by most of the newly synthesized sulfonamides while the glaucoma associated isoform hCA II was moderately inhibited with KIs spanning in low nanomolar range (KI = 8.0 nM-0.903 μM). The membrane bound isoform hCA IV, which is known to be involved in glaucoma and retinitis pigmentosa among others, was strongly inhibited by all newly synthesized sulfonamides out of which nine compounds inhibited isoform hCA IV even more effectively as compared to standard drug acetazolamide (AAZ). The membrane bound isoform hCA IX, associated with growth of tumor cells, was moderately inhibited with KIs ranging between 51 nM-3.198 μM. The effect of appending variously substituted tails on heterocyclic moieties over inhibition potential of synthesized sulfonamides is also disclosed which can be of further interest in pharmacological studies for exploring synthesis of isoform selective inhibitors. SN - 1768-3254 UR - https://www.unboundmedicine.com/medline/citation/31539777/Continued_exploration_and_tail_approach_synthesis_of_benzenesulfonamides_containing_triazole_and_dual_triazole_moieties_as_carbonic_anhydrase_I_II_IV_and_IX_inhibitors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0223-5234(19)30850-5 DB - PRIME DP - Unbound Medicine ER -