Sildenafil is a strong activator of mammalian carbonic anhydrase isoforms I-XIV

ÇOBAN, TAHA ABDULKADİR; BEYDEMIR, Suekrue; Gülçin, İlhami; EKINCI, Deniz; Innocenti, Alessio; Vullo, Daniela; SUPURAN, Claudiu T.

doi:10.1016/j.bmc.2009.07.019

Makale Tam Makale Uluslararası 2009

Sildenafil is a strong activator of mammalian carbonic anhydrase isoforms I-XIV

TAHA ABDULKADİR ÇOBAN, Suekrue BEYDEMIR, İlhami Gülçin, Deniz EKINCI, Alessio Innocenti, Daniela Vullo, Claudiu T. SUPURAN

BIOORGANIC & MEDICINAL CHEMISTRY Cilt 17 · Sayı 16 · ss. 5791–5795 · 15.08.2009

DOI ile aç

Özet

Sildenafil citrate, a phosphodiesterase-5 (PDE5) inhibitor widely used for the treatment of erectile dysfunction was investigated for its interaction with the zinc-enzyme carbonic anhydrase (CA, EC 4.2.1.1), as it has in its molecule a piperazine moiety also found in some CA activators (CAAs). Sildenafil was a potent, low micromolar activator of several CA isozymes, such as CA I, VA and VI (K(A)s in the range of 1.08-6.54 mu M), and activated slightly less the isoforms CA III, IV and VA (K(A)s of 13.4-16.8 mu M). CA isozymes II, IX, XIII and XIV showed activation constants in the range of 27.5-34.0 mu M, whereas the least activated isoforms were CA VII and XII (K(A)s of 72.9-73.0 mu M). Sildenafil citrate was also given orally to Sprague-Dawley rats at 1 mg/kg body weight. Red blood cell CA activity was inhibited in the treated animals at 3-5 h post-administration (in the range of 60-85%), probably due to NO/nitrite formed by PDE5 inhibition or by another, unknown mechanism. Whether CA activation by sildenafil has clinical consequences in humans is beyond the scope of the present work and warrants further studies. (C) 2009 Elsevier Ltd. All rights reserved.

Anahtar kelimeler

SITE carbonic anhydrase INHIBITORS amino acids THERAPEUTIC APPLICATIONS VITRO Isozymes I-XIV ISOZYME-II piperazine Sildenafil citrate Enzyme activator Proton shuttling VII VA PHOSPHODIESTERASE-5 DIURETICS

Atıf için künye

ÇOBAN, T. A., BEYDEMIR, S., Gülçin, İ., EKINCI, D., Innocenti, A., Vullo, D., & SUPURAN, C. T. (2009). Sildenafil is a strong activator of mammalian carbonic anhydrase isoforms I-XIV. BIOORGANIC & MEDICINAL CHEMISTRY, 17(16), 5791–5795. https://doi.org/10.1016/j.bmc.2009.07.019

BibTeX

@article{coban2009-68007,
  author = {ÇOBAN, TAHA ABDULKADİR and BEYDEMIR, Suekrue and Gülçin, İlhami and EKINCI, Deniz and Innocenti, Alessio and Vullo, Daniela and SUPURAN, Claudiu T.},
  title = {Sildenafil is a strong activator of mammalian carbonic anhydrase isoforms I-XIV},
  journal = {BIOORGANIC & MEDICINAL CHEMISTRY},
  year = {2009},
  volume = {17},
  number = {16},
  pages = {5791--5795},
  issn = {0968-0896},
  doi = {10.1016/j.bmc.2009.07.019},
  url = {https://akademik.atauni.edu.tr/yayinlar/68007-sildenafil-is-a-strong-activator-of-mammalian-carbonic-anhydrase-isoforms-i-xiv}
}