Synthesis, cytotoxicities, and carbonic anhydrase inhibition potential of 6-(3-aryl-2-propenoyl)-2(3H)-benzoxazolones

• Published in: Journal of enzyme inhibition and medicinal chemistry Vol. 34; no. 1; pp. 1722 - 1729
• Main Authors: Bilginer, Sinan, Gul, Halise Inci, Erdal, Feyza Sena, Sakagami, Hiroshi, Levent, Serkan, Gulcin, Ilhami, Supuran, Claudiu T.
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01-01-2019; Taylor & Francis Group
• Subjects: Anticancer; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antineoplastic Agents - toxicity; Benzoxazoles - chemical synthesis; Benzoxazoles - chemistry; Benzoxazoles - pharmacology; Benzoxazoles - toxicity; benzoxazolone; carbonic anhydrase; Carbonic Anhydrase Inhibitors - chemical synthesis; Carbonic Anhydrase Inhibitors - chemistry; Carbonic Anhydrase Inhibitors - pharmacology; Carbonic Anhydrase Inhibitors - toxicity; Carbonic Anhydrases - metabolism; Cell Line, Tumor; Cell Survival - drug effects; chalcone; Chalcone - chemistry; Child; cytotoxic; Drug Screening Assays, Antitumor - methods; Female; Humans; Isoenzymes - metabolism; Molecular Structure; Original; Structure-Activity Relationship; chalcone; carbonic anhydrase; Anticancer; cytotoxic; benzoxazolone
• ISSN: 1475-6366; 1475-6374
• DOI: 10.1080/14756366.2019.1670657

In this study, new chalcone compounds having the chemical structure of 6-(3-aryl-2-propenoyl)-2(3H)-benzoxazolones (1-8) were synthesised and were characterised by
1
H-NMR,
13 
C-NMR, and HRMS spectra. Cytotoxic and carbonic anhydrase (CA) inhibitory effects of the compounds were investigated. Cytotoxicity results pointed out that compound 4, 6-[3-(4-trifluoromethylphenyl)-2-propenoyl]-3H-benzoxazol-2-one, showed the highest cytotoxicity (CC
50
) and potency-selectivity expression (PSE) value, and thus can be considered as a lead compound of this study. According to the CA inhibitory results, IC
50
values of the compounds 1-8 towards hCA I were in the range of 29.74-69.57 µM, while they were in the range of 18.14 - 48.46 µM towards hCA II isoenzyme. K
i
values of the compounds 1-8 towards hCA I were in the range of 28.37 ± 6.63-70.58 ± 6.67 µM towards hCA I isoenzyme and they were in the range of 10.85 ± 2.14 - 37.96 ± 2.36 µM towards hCA II isoenzyme.