The solvent-controlled regioselective synthesis of 3-amino-5-aryl-rhodanines as novel inhibitors of human carbonic anhydrase enzymes

Ozer E. B., ÇAĞLAYAN C., Bayindir S.

Tetrahedron, cilt.120, 2022 (SCI-Expanded) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 120
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1016/j.tet.2022.132896
  • Dergi Adı: Tetrahedron
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, Veterinary Science Database
  • Anahtar Kelimeler: 3-amino-rhodanine, 5-substitüe-rhodanine, Carbonic anhydrase, Catalyst-free reaction, Enzyme inhibition, Knoevenagel condensation
  • Bilecik Şeyh Edebali Üniversitesi Adresli: Evet

Özet

The regioselective functionalization from C5-position instead of more nucleophilic NH2 of 3-NH2-Rh (1) via a green approach is representing a challenge. The primary goal of this study is to develop the solvent-promoted and -controlled regioselective bond alkylation reactions of 3-NH2-Rh (1) with NH2 free-rhodanine (1) under catalyst-free conditions. In the presence of water as the solvent, C5-addition arylation reactions of 3-NH2-Rh (1) with aldehydes efficiently gave C5-arylated-rhodanine (5-Ar-Rhs). On the other hand, using catalytic amounts of an acid catalyst in ethanol, the reaction of 3-NH2-Rh (1) and aldehydes resulted in the arylation of rhodanine at the NH-position. Water plays two roles in the reactions: converting the 3-NH2-Rh (1) into bidentate nucleophiles and activating the C-5 position of 3-NH2-Rh (1) to achieve the Knoevenagel condensation via hydrogen bond clusters. The 3-NH2-Rh (1) act as a C-nucleophile due to the H-bond clusters between water and the amino group of 3-NH2-Rh (1), whereas upon using catalytic amounts of CH3CO2H in pure ethanol the compounds act as an NH2-nucleophile. Moreover, the enzyme inhibition studies of novel 5-Ar-Rhs against cytosolic carbonic anhydrase (hCAs) I, and II isoforms was carried out. As a result of these biological studies, inhibition constants (Ki) for hCA I and hCA II were found in the range of 239.88 ± 79.31 to 610.24 ± 111.43 nM, and 262.69 ± 13.20 to 638.10 ± 127.73 nM, respectively.