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Makale Tam Makale Uluslararası 2021

Comprehensive study on potent and selective carbonic anhydrase inhibitors: Synthesis, bioactivities and molecular modelling studies of 4-(3-(2-arylidenehydrazine-1-carbonyl)-5-(thiophen-2-yl)-1H-pyrazole-1-yl) benzenesulfonamides

CEM YAMALI, Hiroshi Sakagami, Yoshihiro Uesawa, Kota Kurosaki, Keitaro Satoh, Yoshiko Masuda, Satoshi Yokose, Abdulilah Ece, Silvia Bua, Andrea Angeli, Claudiu T. Supuran, Halise İnci Gül

European journal of medicinal chemistry Cilt 217 · 01.05.2021
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Özet

In this research, rational design, synthesis, carbonic anhydrases (CAs) inhibitory effects, and cytotoxicities of the 4-(3-(2-arylidenehydrazine-1-carbonyl)-5-(thiophen-2-yl)-1H-pyrazole-1-yl)benzenesulfonamides 1-20 were reported. Compound 18 (Ki = 7.0 nM) was approximately 127 times more selective cancer-associated hCA IX inhibitor over hCA I, while compound 17 (Ki = 10.6 nM) was 47 times more selective inhibitor of hCA XI over hCA II compared to the acetazolamide. Compounds 11 (CC50 = 5.2 mM) and 20 (CC50 = 1.6 mM) showed comparative tumor-specificity (TS= > 38.5; >128.2) with doxorubicin (TS > 43.0) towards HSC-2 cancer cell line. Western blot analysis demonstrated that 11 induced slightly apoptosis whereas 20 did not induce detectable apoptosis. A preliminary analysis showed that some correlation of tumor-specificity of 1-20 with the chemical descriptors that reflect hydrophobic volume, dipole moment, lowest hydrophilic energy, and topological structure. Molecular docking simulations were applied to the synthesized ligands to elucidate the predicted binding mode and selectivity profiles towards hCA I, hCA II, and hCA IX. (C) 2021 Elsevier Masson SAS. All rights reserved.

Anahtar kelimeler

EXPRESSION carbonic anhydrase apoptosis cytotoxicity anticancer Mannich bases DOCKING Benzenesulfonamide hCA IX OSCC Pyrazole SULFONAMIDES metastasis Hydrazone hCA II IX XII DRUG DESIGN HYDRAZONES

Sürdürülebilir Kalkınma Amaçları

  • SKA 3: Sağlıklı Bireyler

Atıf için künye

YAMALI, C., Sakagami, H., Uesawa, Y., Kurosaki, K., Satoh, K., Masuda, Y., Yokose, S., Ece, A., Bua, S., Angeli, A., Supuran, C. T., & Gül, H. İ. (2021). Comprehensive study on potent and selective carbonic anhydrase inhibitors: Synthesis, bioactivities and molecular modelling studies of 4-(3-(2-arylidenehydrazine-1-carbonyl)-5-(thiophen-2-yl)-1H-pyrazole-1-yl) benzenesulfonamides. European journal of medicinal chemistry, 217. https://doi.org/10.1016/j.ejmech.2021.113351

BibTeX 
@article{yamali2021-19986,
  author = {YAMALI, CEM and Sakagami, Hiroshi and Uesawa, Yoshihiro and Kurosaki, Kota and Satoh, Keitaro and Masuda, Yoshiko and Yokose, Satoshi and Ece, Abdulilah and Bua, Silvia and Angeli, Andrea and Supuran, Claudiu T. and Gül, Halise İnci},
  title = {Comprehensive study on potent and selective carbonic anhydrase inhibitors: Synthesis, bioactivities and molecular modelling studies of 4-(3-(2-arylidenehydrazine-1-carbonyl)-5-(thiophen-2-yl)-1H-pyrazole-1-yl) benzenesulfonamides},
  journal = {European journal of medicinal chemistry},
  year = {2021},
  volume = {217},
  issn = {0223-5234},
  doi = {10.1016/j.ejmech.2021.113351},
  url = {https://akademik.atauni.edu.tr/yayinlar/19986-comprehensive-study-on-potent-and-selective-carbonic-anhydrase-inhibitors}
}