New halogenated chalcones with cytotoxic and carbonic anhydrase inhibitory properties: 6-(3-Halogenated phenyl-2-propen-1-oyl)-2(3H)-benzoxazolones

BİLGİNER S., GÜL H. İ., Erdal F. S., Sakagami H., GÜLÇİN İ.

Archiv der Pharmazie, cilt.353, sa.6, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 353 Sayı: 6
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1002/ardp.201900384
  • Dergi Adı: Archiv der Pharmazie
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chimica, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: benzoxazolone, carbonic anhydrase, cytotoxicity, halogenated chalcone, PHENOLIC MANNICH-BASES, BIOLOGICAL EVALUATION, POTENT ACTIVITY, IN-VITRO, HCA I, DERIVATIVES, DESIGN, ACETYLCHOLINESTERASE, BIOACTIVITIES, ANTIFUNGAL
  • Atatürk Üniversitesi Adresli: Evet

Özet

In this study, novel halogenated chalcones, 6-(3-halogenated phenyl-2-propen-1-one)-2(3H)-benzoxazolones (2a-n), were synthesized for the first time (except 2a), and their chemical structures were characterized by H-1 nuclear magnetic resonance (NMR), C-13 NMR, and high-resolution mass spectrometry spectra. Cytotoxic activities and carbonic anhydrase (CA) inhibitory effects of the compounds were studied to identify new possible drug candidate molecules. Cytotoxicity results pointed out that compound 2m, 6-[3-(3-bromophenyl)-2-propenoyl]-2(3H)-benzoxazolone, had the highest cytotoxicity (CC50) and potency selectivity expression (PSE) values. Thus, compound 2m can be considered as a lead compound of the series in terms of cytotoxicity. When the CA inhibition results of the compounds were evaluated, it was found that the K-i values of the compounds ranged from 30.5 +/- 11.3 to 65.5 +/- 25.6 mu M toward hCA I, and they ranged from 7.3 +/- 1.8 to 58.8 +/- 12.3 mu M toward hCA II. However, the K-i values of the reference drug, acetazolamide (AZA), were 30.2 +/- 7.8 and 4.4 +/- 0.6 mu M toward hCA I and hCA II, respectively. According to the results obtained, compounds 2a-n had lower K-i values than AZA, whereas compounds 2a, 2b, 2e-g, 2l, and 2n had similar K-i values, compared with AZA. So, the compounds 2a, 2b, 2e-g, 2l, and 2n can be considered as lead molecules of this series for further considerations.