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

Abstract

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 ¹H-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 (CC₅₀) and potency-selectivity expression (PSE) value, and thus can be considered as a lead compound of this study. According to the CA inhibitory results, IC₅₀ 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.

Keywords: Anticancer; benzoxazolone; carbonic anhydrase; chalcone; cytotoxic.

Scheme 1.

Synthesis of the compounds 1–8. Ar: Phenyl (1); 4-methylphenyl (2); 4-Methoxyphenyl (3); 4-trifluoromethylphenyl (4); 3-hyrdoxyphenyl (5); 4-isopropylphenyl (6); 4-dimethylaminophenyl (7); 4-benzyloxyphenyl (8).

Figure 1.

The details of ¹H-NMR spectra of compound 2 as represantative ¹H-NMR. δ (ppm) H_a: 8.05 (dd, 1H, J_Ha-Hb: 8.1 Hz, J_Ha-Hc: 1.5 Hz), H_b: 7.22 (d, 1H, J_Ha-Hb: 8.1 Hz), H_c: 8.08 (d, 1H, J_Ha-Hc: 1.5 Hz), H_d: 7.79 (d, 2H, J_Hd-He: 8.0 Hz), H_e: 7.27 (d, 2H, J_Hd-He: 8.0 Hz), H_α: 7.93 (d, 1H, J_Hα-Hβ: 15.5 Hz), H_β: 7.70 (d, 1H, J_Hα-Hβ: 15.5 Hz) CH₃ protons: 2.35 (s, 3H).