Synthesis and biological evaluation of novel propargylquinobenzothiazines and their derivatives as potential antiproliferative, anti-inflammatory, and anticancer agents

Figures & data

Scheme 1. Synthesis of quinobenzothiazines 4–6 and diquinothiazines 9 and 10.

Table 1. Effects of the compounds on PBMC survival, PHA-induced blood lymphocyte proliferation and TNF-α production by whole blood cultures. NT, not toxic.

	Cytotoxicity (%)		Antiproliferative activity (% inhibition)		TNF-α inhibition (%)
	μg/mL
Compound	10	1	10	1	5	1	0.1
5a	36.0	NT	94.7	56.7	80.2	56.0	36.3
5b	28.7	4.14	87.9	45.5	75.2	53.8	31.7
5c	34.8	NT	82.5	35.1	71.1	59.6	32.7
5d	23.5	NT	69.0	33.5	67.3	59.1	39.2
5e	2.3	NT	41.1	22.0	64.7	48.2	17.3
5f	28.4	NT	91.0	52.5	75.2	40.3	9.0
5g	29.2	NT	90.0	50.3	57.5	35.5	17.9
5h	25.6	3.82	82.9	44.9	73.8	59.1	42.1
6a	24.5	NT	94.2	28.7	61.6	39.8	31.0
6b	21.7	NT	92.2	23.4	58.5	40.0	13.2
6c	9.3	NT	80.9	20.2	49.1	55.1	23.5
10	18.5	NT	76.1	45.6	57.0	64.0	52.7

Table 2. Inhibitory effects of the compounds on growth of SW-984 and L-1210 cell lines. The results represent mean IC₅₀ values from three independent experiments.

	IC50 μg/mL
Compound	SW-984	L-1210
5d	3.8	1.4
5e	10.7	11.5
5g	13.8	1.2
10	12.7	2,6
Cisplatin	8.6	0.3

Table 3. Effect of 5e compound on expresion of caspases in Jurkat and L-1210 cell lines.

Cell line	Protein	DMSO	5e
Jurkat	β-Actin	1	1
	Caspase-3	0.686	0
	Caspase-9	0.895	0.728
	Caspase-9	0.829	0.706
L1210	β-Actin	1	1
	Caspase-3	0.979	0.500
	Caspase-8	0.940	0.528
	Caspase-9	1.032	0.494