Novel 2-indolinones containing a sulfonamide moiety as selective inhibitors of candida beta-carbonic anhydrase enzyme

AKDEMİR A., Angeli A., Goektas F., Eraslan Elma P., Karali N. L., Supuran C. T.

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, cilt.34, sa.1, ss.528-531, 2019 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 34 Sayı: 1
  • Basım Tarihi: 2019
  • Doi Numarası: 10.1080/14756366.2018.1564045
  • Dergi Adı: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.528-531
  • Anahtar Kelimeler: Sulfonamides, Candida glabrata, carbonic anhydrase, docking, VIBRIO-CHOLERAE, BACTERIAL, ISATIN, ALPHA, RESISTANCE, GLABRATA, ALBICANS, BINDING, POTENT, LIGHT
  • İstanbul Üniversitesi Adresli: Evet

Özet

Inhibition of the beta-carbonic anhydrase (CA, EC 4.2.1.1) from pathogenic Candida glabrata (CgNce103) by 1H-indole-2,3-dione 3-[N-(4-sulfamoylphenyl)thiosemicarbazones] 4a-m was investigated. All the compounds were found to be potent inhibitors of CgNce103, with inhibition constants in the range of 6.4-63.9 nM. The 5,7-dichloro substituted derivative 4l showed the most effective inhibition (K-I of 6.4 nM) as well as the highest selectivity for inhibiting CgNce103 over the cytosolic human (h) isoforms hCA I and II. A possible binding interaction of compound 4l within the active site of CgNce103 has been proposed based on docking studies.