| Yazarlar (7) |
Nabıh Lolak
Türkiye |
|
Cüneyt Türkeş
Erzincan Binali Yıldırım Üniversitesi, Türkiye |
|
Süleyman Akocak
Türkiye |
Doç. Dr. Hatice Esra DURAN
Kafkas Üniversitesi, Türkiye |
|
Mesut Işık
Bilecik Şeyh Edebali Üniversitesi, Türkiye |
|
Mustafa Durgun
Harran Üniversitesi, Türkiye |
|
Şükrü Beydemir
Anadolu Üniversitesi, Türkiye |
| Özet |
| Sulfonamides, recognized as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors, are crucial in treating diverse diseases, including epilepsy, glaucoma, bacterial infections, and various pathological processes, e.g., high blood pressure, rheumatoid arthritis, ulcerative colitis, pain, and inflammation. Additionally, therapeutically, 1,3-diaryl-substituted triazenes and sulphamethazines (SM) are integral components in various drug structures, and the synthesis of novel compounds within these two categories holds substantial significance. Herein, ten 1,3-diaryltriazene-substituted sulphamethazine derivatives SM(1-10), which were created by reacting the diazonium salt of sulphamethazine with substituted aromatic amines, were synthesized and the physiologically and pharmacologically relevant human (h) isoforms hCA I and II, cytosolic isozymes, were included in the study. The synthesized compounds showed excellent inhibition versus hCAs; the 4-butoxy (SM7, K of 5.69 ± 0.59 nM) compound exhibited a potent inhibitory effect against the hCA I compared with the reference drug acetazolamide (AAZ, K of 116.00 ± 8.48 nM). The 4-cyano (SM4, K of 5.87 ± 0.57 nM) compound displayed higher potency than AAZ (K of 57.25 ± 4.15 nM) towards hCA II. Meanwhile, among the synthesized molecules, the 3,4-dimethoxy (SM9, K of 74.98 ± 10.49 nM, S of 9.94) compound (over hCA I) displayed a noticeable selectivity for hCA isoform II. The target compounds in the molecular docking investigation were determined to take part in various hydrophilic and hydrophobic interactions with nearby amino acids and fit nicely into the active sites of the hCAs. This research has yielded compounds displaying varying affinity toward hCA isoenzymes, ultimately serving as potent and selective hCA inhibitors. Given its substantial biological inhibitory potency, this particular derivative series is determined to hold the potential to serve as a promising lead compound against these hCAs. |
| Anahtar Kelimeler |
| Carbonic anhydrase | Triazene | Sulphamethazine | Selective inhibitor | In silico study |
| Makale Türü | Özgün Makale |
| Makale Alt Türü | SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale |
| Dergi Adı | Archives of Biochemistry and Biophysics |
| Dergi ISSN | 0003-9861 Wos Dergi Scopus Dergi |
| Dergi Tarandığı Indeksler | SCI-Expanded |
| Dergi Grubu | Q1 |
| Makale Dili | Türkçe |
| Basım Tarihi | 11-2024 |
| Cilt No | 761 |
| Doi Numarası | 10.1016/j.abb.2024.110181 |
| Makale Linki | https://doi.org/10.1016/j.abb.2024.110181 |
| Atıf Sayıları | |
| WoS | 4 |
| Google Scholar | 5 |
