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 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 mM, while they were in the range of 18.14-48.46 mM 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 mM towards hCA I isoenzyme and they were in the range of 10.85 ± 2.14-37.96 ± 2.36 mM towards hCA II isoenzyme.

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

“…Therefore, the compounds were also evaluated against HGF and HPLF nonmalignant cells, as normal cells surround the tumor cells in an organism. Therefore, tumor selectivity (TS) values were calculated by dividing the average CC 50 value toward normal cells by the average CC 50 value toward cancer cell lines as reported [ 3,28,40,44,51,64,65 ] (Table 1). According to results, the TS values of all compounds were >1, which implies that they were all tumor‐selective compounds.…”

“…To identify the most promising compounds in terms of both high potencies and selective cytotoxicities, the PSE values have been defined and calculated, as shown in our previous studies. [ 3,39–41,63–65 ] PSE values of the compounds were in the range of 9–158 (Table 1). The PSE values of the compounds in the series were >30, except compounds 2a , 2e , and 2h .…”

“…The precipitated crude product was filtered and air‐dried, and crystallized from ethanol. [ 3 ] (Yield: 77%, m.p: 231–234°C, brown crystals.) [ 3,58 ]…”

“…[ 2 ] Anticancer drugs in clinics have low selectivity, drug resistance problem, and side effects such as vomiting, hair loss, and pain. [ 3 ] Thus, the researchers are focusing on the development of new anticancer drug candidates that have high selectivity and low toxicity.…”

“…In a very limited number of studies, some chalcones bearing 2(3 H )‐benzoxazolone with different substituents on the phenyl ring were reported with their strong cytotoxic activities. [ 3,58,61,62 ] Both the selective and strong anticancer activities of these compounds pointed out the importance of this chemical moiety in designing new chalcone compounds for possible drug candidate molecules. Thus, we chose the chalcone structure bearing the 2(3 H )‐benzoxazolone heterocycle as the main chemical skeleton for further investigation.…”