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Inhibition of human carbonic anhydrase isozymes I, II, IX and XII with a new series of sulfonamides incorporating aroylhydrazone-, [1,2,4]triazolo[3,4-b][1,3,4]thiadiazinyl- or 2-(cyanophenylmethylene)-1,3,4-thiadiazol-3(2H)-yl moieties.
J Enzyme Inhib Med Chem. 2015 Feb; 30(1):52-6.JE

Abstract

A series of benzenesulfonamides incorporating aroylhydrazone, piperidinyl, sulfone, [1,2,4]triazolo[3,4-b][1,3,4]thiadiazinyl- or 2-(cyanophenyl-methylene)-1,3,4-thiadiazol-3(2H)-yl moieties was investigated as inhibitors of four α-carbonic anhydrases (CAs, EC 4.2.1.1), the human (h) isoforms hCA I, II (cytosolic, offtarget enzymes) and hCA IX and XII (transmembrane, tumor-associated isoforms). Low nanomolar activity was observed against hCA II (KIs of 0.56-17.1 nM) with these sulfonamides, whereas the slow cytosolic isoform hCA I was less inhibited by these compounds (KIs of 86.4 nM-32.8 µM). Most of these sulfonamides significantly inhibited CA IX, with KIs in the range of 4.5-47.0 nM, although some of the derivatives incorporating bulkier bicyclic moieties, as well as 2-thienyl fragments, showed a weaker activity against this isoform (KIs in the range 50.1-553 nM). All the investigated compounds also inhibited CA XII with KIs in the range 0.85-376 nM. The best inhibitors were those incorporating bulky [1,2,4]triazolo[3,4-b][1,3,4]thiadiazinyl moieties and 1,3,4-thiadiazol-3(2H)-yl groups.

Authors+Show Affiliations

Department of Pharmaceutical Chemistry, College of Pharmacy, Salman bin Abdulaziz University , Alkharj , Saudi Arabia .No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24666294

Citation

Alafeefy, Ahmed M., et al. "Inhibition of Human Carbonic Anhydrase Isozymes I, II, IX and XII With a New Series of Sulfonamides Incorporating Aroylhydrazone-, [1,2,4]triazolo[3,4-b][1,3,4]thiadiazinyl- or 2-(cyanophenylmethylene)-1,3,4-thiadiazol-3(2H)-yl Moieties." Journal of Enzyme Inhibition and Medicinal Chemistry, vol. 30, no. 1, 2015, pp. 52-6.
Alafeefy AM, Abdel-Aziz HA, Vullo D, et al. Inhibition of human carbonic anhydrase isozymes I, II, IX and XII with a new series of sulfonamides incorporating aroylhydrazone-, [1,2,4]triazolo[3,4-b][1,3,4]thiadiazinyl- or 2-(cyanophenylmethylene)-1,3,4-thiadiazol-3(2H)-yl moieties. J Enzyme Inhib Med Chem. 2015;30(1):52-6.
Alafeefy, A. M., Abdel-Aziz, H. A., Vullo, D., Al-Tamimi, A. M., Awaad, A. S., Mohamed, M. A., Capasso, C., & Supuran, C. T. (2015). Inhibition of human carbonic anhydrase isozymes I, II, IX and XII with a new series of sulfonamides incorporating aroylhydrazone-, [1,2,4]triazolo[3,4-b][1,3,4]thiadiazinyl- or 2-(cyanophenylmethylene)-1,3,4-thiadiazol-3(2H)-yl moieties. Journal of Enzyme Inhibition and Medicinal Chemistry, 30(1), 52-6. https://doi.org/10.3109/14756366.2013.877897
Alafeefy AM, et al. Inhibition of Human Carbonic Anhydrase Isozymes I, II, IX and XII With a New Series of Sulfonamides Incorporating Aroylhydrazone-, [1,2,4]triazolo[3,4-b][1,3,4]thiadiazinyl- or 2-(cyanophenylmethylene)-1,3,4-thiadiazol-3(2H)-yl Moieties. J Enzyme Inhib Med Chem. 2015;30(1):52-6. PubMed PMID: 24666294.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of human carbonic anhydrase isozymes I, II, IX and XII with a new series of sulfonamides incorporating aroylhydrazone-, [1,2,4]triazolo[3,4-b][1,3,4]thiadiazinyl- or 2-(cyanophenylmethylene)-1,3,4-thiadiazol-3(2H)-yl moieties. AU - Alafeefy,Ahmed M, AU - Abdel-Aziz,Hatem A, AU - Vullo,Daniela, AU - Al-Tamimi,Abdul-Malek S, AU - Awaad,Amani S, AU - Mohamed,Menshawy A, AU - Capasso,Clemente, AU - Supuran,Claudiu T, Y1 - 2014/03/25/ PY - 2014/3/27/entrez PY - 2014/3/29/pubmed PY - 2015/9/16/medline KW - Cancer-associated isoform KW - carbonic anhydrase KW - enzyme inhibitor KW - sulfonamide SP - 52 EP - 6 JF - Journal of enzyme inhibition and medicinal chemistry JO - J Enzyme Inhib Med Chem VL - 30 IS - 1 N2 - A series of benzenesulfonamides incorporating aroylhydrazone, piperidinyl, sulfone, [1,2,4]triazolo[3,4-b][1,3,4]thiadiazinyl- or 2-(cyanophenyl-methylene)-1,3,4-thiadiazol-3(2H)-yl moieties was investigated as inhibitors of four α-carbonic anhydrases (CAs, EC 4.2.1.1), the human (h) isoforms hCA I, II (cytosolic, offtarget enzymes) and hCA IX and XII (transmembrane, tumor-associated isoforms). Low nanomolar activity was observed against hCA II (KIs of 0.56-17.1 nM) with these sulfonamides, whereas the slow cytosolic isoform hCA I was less inhibited by these compounds (KIs of 86.4 nM-32.8 µM). Most of these sulfonamides significantly inhibited CA IX, with KIs in the range of 4.5-47.0 nM, although some of the derivatives incorporating bulkier bicyclic moieties, as well as 2-thienyl fragments, showed a weaker activity against this isoform (KIs in the range 50.1-553 nM). All the investigated compounds also inhibited CA XII with KIs in the range 0.85-376 nM. The best inhibitors were those incorporating bulky [1,2,4]triazolo[3,4-b][1,3,4]thiadiazinyl moieties and 1,3,4-thiadiazol-3(2H)-yl groups. SN - 1475-6374 UR - https://www.unboundmedicine.com/medline/citation/24666294/Inhibition_of_human_carbonic_anhydrase_isozymes_I_II_IX_and_XII_with_a_new_series_of_sulfonamides_incorporating_aroylhydrazone__[124]triazolo[34_b][134]thiadiazinyl__or_2__cyanophenylmethylene__134_thiadiazol_3_2H__yl_moieties_ L2 - https://www.tandfonline.com/doi/full/10.3109/14756366.2013.877897 DB - PRIME DP - Unbound Medicine ER -