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

Figures & data

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).

Table 1. Cytotoxic activities of the compounds 1–8 towards human OSCC cell lines and human oral normal cells

	CC50(μM)
	OSCC		Human normal oral cells
	HSC-2	SD	HGF	SD	HPLF	SD	Mean	TS	PSE
Compounds	(A)						(B)	(B/A)	(B/A2)×100
1	22.1	1.2	71.0	9.5	83.3	14.0	77.2	3.5	16
2	10.1	0.4	87.7	18.5	105.3	3.1	96.5	9.5	94
3	14.5	2.9	88.3	17.9	84.0	0.0	86.2	5.9	41
4	4.0	0.6	24.7	0.6	26.3	0.5	25.5	6.4	159
5	6.9	0.5	55.4	19.7	50.3	3.5	52.9	7.7	111
6	10.1	0.5	53.0	5.3	76.0	7.0	64.5	6.4	64
7	30.2	3.2	76.3	9.3	70.0	2.0	73.2	2.4	8
8	11.9	0.2	98.0	50.2	32.7	1.5	65.3	5.5	46
5-FU*	37.7	0.0	>1000	0.0	>1000	0.0	>1000	>28.3	80.7
DXR*	0.5	0.1	0.7	0.0	>10	0.0	>5.3	>10.4	>2030

^* 5-Fluorouracil (5-FU) and Doxorubicin (DXR) were used as reference drugs.

SD: standard deviation.

Table 2. Inhibitory effects of the compounds 1–8 on hCA I and hCA II isoenzymes.

	IC50 (µM)			Ki (µM)
Compounds	hCA I	r^2	hCA II	r^2	hCA I	hCA II
1	58.72	0.9613	40.53	0.9392	70.58 ± 6.67	36.16 ± 13.35
2	33.00	0.9546	45.59	0.9786	38.80 ± 1.93	32.12 ± 6.60
3	47.46	0.9406	48.13	0.9854	30.49 ± 11.26	36.20 ± 10.26
4	29.74	0.9397	45.0	0.9778	30.75 ± 3.49	19.2 ± 2.19
5	69.57	0.9375	48.46	0.9509	63.04 ± 15.45	35.20 ± 8.36
6	52.11	0.9496	30.13	0.9356	37.05 ± 7.77	33.29 ± 6.15
7	40.29	0.9533	29.74	0.9538	52.25 ± 9.97	10.85 ± 2.14
8	57.75	0.9509	18.14	0.9397	28.37 ± 6.63	37.96 ± 2.36
AZA*	16.58	0.9887	8.37	0.9825	30.18 ± 7.77	4.41 ± 0.55

^* Acetazolamide (AZA) was used as a standard inhibitor for both hCA I and II isoenzymes. r²: is a statistical measure of how close the data are to the fitted regression line. It is also known as the coefficient of determination, or the coefficient of multiple determinations for multiple regressions⁵⁹.

Gul HI, Tugrak M, Gul M, et al. New phenolic Mannich bases with piperazines and their bioactivities. Bioorg Chem 2019;90:103057.

 PubMed Web of Science ®Google Scholar