Design, Synthesis and Bioactivity of Chalcone Derivative Containing Quinazolinone

doi:10.6023/cjoc202301020

Abstract

Twenty-five chalcone derivatives containing quinazolinone were designed and synthesized. The results of antiviral biological experiments showed that (E)-3-(4-chlorophenyl)-6-fluoro-2-((2-(4-(3-(4-methoxyphenyl)acryloyl)phenoxy)ethyl)- thio)quinazolin-4(3H)-one (Z12) had a good inhibitory activity against tobacco mosaic virus (TMV), and the EC₅₀ values of treatment and protection were 94.3 and 98.8 μg/mL, respectively, which were better than those of ningamycin (NNM, 216.1 and 189.6 μg/mL). The results of transmission electron microscope showed that Z12 broke TMV virus particles and formed rod structures of different lengths. The results of microscale thermophoresis experiment (MST) showed that the K_d value of Z12 binding to tobacco mosaic virus coat protein (TMV-CP) was (0.033±0.014) μmol/L. The K_d value of Z12 was better than that of ningnanmycin [(0.106±0.024) μmol/L], which indicated that Z12 had stronger binding ability to TMV-CP. The antibacterial test results showed that some compounds showed excellent activity against Xanthomonas oryzae pv. Oryzae (Xoo) and Xanthomonas axonopodis pv.Citri (Xac), among which ((E)-2-((2-(4-(3-(4-bromophenyl)acryloyl)phenoxy)ethyl)thio)-3- (4-chlorophenyl)-6-nitroquinazolin-4(3H)-one (Z25) showed the best activity against Xoo. The EC₅₀ value of Xoo was 19.5 μg/mL, which was better than those of bismerthiazol (77.1 μg/mL) and thiodiazole copper (95.9 μg/mL). The results of scanning electron microscope showed that the cell membrane of Xoo was shriveled and deformed after Z25 treatment. The experimental results showed that chalcone derivatives containing quinazolinone were potential antiviral and antibacterial drugs.

Key words: quinazolinone, chalcone, organic synthesis, antibacterial, antiviral

Cite this article

Ran Zhou, Chunmei Yuan, Tao Zhang, Piao Mao, Yi Liu, Kaini Meng, Hui Xin, Wei Xue. Design, Synthesis and Bioactivity of Chalcone Derivative Containing Quinazolinone[J]. Chinese Journal of Organic Chemistry, 2023, 43(9): 3196-3209.

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Compd.	Curative activity/%	Protective activity/%	Inactivation activity/%	Compd.	Curative activity/%	Protective activity/%	Inactivation activity/%
Z1	31.5±4.6	17.9±3.4	37.5±0.8	Z19	25.1±1.1	45.8±0.7	53.1±4.2
Z2	32.3±2.7	56.3±3.0	32.3±2.7	Z20	62.5±2.9	35.5±1.3	47.6±3.2
Z3	44.8±0.4	45.8±2.5	44.8±0.4	Z21	52.3±3.5	55.7±2.4	58.5±3.3
Z4	51.2±2.2	35.8±2.5	23.0±1.9	Z22	24.7±2.7	36.9±0.9	64.7±3.9
Z5	66.9±3.2	67.4±1.1	39.8±0.2	Z23	17.9±2.3	20.1±1.7	38.1±1.6
Z6	34.7±2.1	44.1±3.4	33.6±0.8	Z24	36.6±2.5	18.9±2.3	28.1±1.2
Z7	26.2±2.1	71.1±0.9	26.2±2.1	Z25	22.2±1.8	27.7±2.9	54.1±2.8
Z8	34.6±2.6	55.9±3.1	46.8±1.8	K1	25.5±1.1	32.1±2.0	33.7±1.4
Z9	22.8±4.1	51.1±0.8	26.9±1.8	K2	35.3±2.3	27.9±1.5	42.1±1.1
Z10	45.6±3.7	63.0±1.9	45.6±3.7	K3	38.7±1.4	35.6±2.0	23.3±0.9
Z11	36.6±4.9	23.0±2.9	36.6±4.9	K4	27.3±1.2	30.1±2.3	34.5±1.5
Z12	66.6±2.9	70.4±2.7	69.5±1.3	K5	40.2±2.3	34.4±1.7	37.5±1.2
Z13	35.0±4.1	33.7±1.1	25.0±4.1	C1	33.9±1.7	24.3±2.1	35.9±1.3
Z14	32.3±1.2	34.6±2.2	61.5±1.3	C2	29.9±2.0	35.8±1.6	27.9±2.1
Z15	28.7±1.1	59.8±2.5	31.5±0.9	C3	39.9±1.6	32.2±1.4	31.1±2.0
Z16	19.8±0.8	38.9±1.0	63.4±2.9	C4	43.3±1.9	33.2±1.6	26.6±1.0
Z17	30.2±1.5	28.6±1.2	67.7±2.4	C5	28.4±1.2	36.4±1.0	38.9±2.3
Z18	22.9±2.1	32.9±2.5	38.3±2.0	NNM^b	59.7±0.7	65.4±2.4	84.1±1.3

Compd.	Curative activity/%	Protective activity/%	Inactivation activity/%	Compd.	Curative activity/%	Protective activity/%	Inactivation activity/%
Z1	31.5±4.6	17.9±3.4	37.5±0.8	Z19	25.1±1.1	45.8±0.7	53.1±4.2
Z2	32.3±2.7	56.3±3.0	32.3±2.7	Z20	62.5±2.9	35.5±1.3	47.6±3.2
Z3	44.8±0.4	45.8±2.5	44.8±0.4	Z21	52.3±3.5	55.7±2.4	58.5±3.3
Z4	51.2±2.2	35.8±2.5	23.0±1.9	Z22	24.7±2.7	36.9±0.9	64.7±3.9
Z5	66.9±3.2	67.4±1.1	39.8±0.2	Z23	17.9±2.3	20.1±1.7	38.1±1.6
Z6	34.7±2.1	44.1±3.4	33.6±0.8	Z24	36.6±2.5	18.9±2.3	28.1±1.2
Z7	26.2±2.1	71.1±0.9	26.2±2.1	Z25	22.2±1.8	27.7±2.9	54.1±2.8
Z8	34.6±2.6	55.9±3.1	46.8±1.8	K1	25.5±1.1	32.1±2.0	33.7±1.4
Z9	22.8±4.1	51.1±0.8	26.9±1.8	K2	35.3±2.3	27.9±1.5	42.1±1.1
Z10	45.6±3.7	63.0±1.9	45.6±3.7	K3	38.7±1.4	35.6±2.0	23.3±0.9
Z11	36.6±4.9	23.0±2.9	36.6±4.9	K4	27.3±1.2	30.1±2.3	34.5±1.5
Z12	66.6±2.9	70.4±2.7	69.5±1.3	K5	40.2±2.3	34.4±1.7	37.5±1.2
Z13	35.0±4.1	33.7±1.1	25.0±4.1	C1	33.9±1.7	24.3±2.1	35.9±1.3
Z14	32.3±1.2	34.6±2.2	61.5±1.3	C2	29.9±2.0	35.8±1.6	27.9±2.1
Z15	28.7±1.1	59.8±2.5	31.5±0.9	C3	39.9±1.6	32.2±1.4	31.1±2.0
Z16	19.8±0.8	38.9±1.0	63.4±2.9	C4	43.3±1.9	33.2±1.6	26.6±1.0
Z17	30.2±1.5	28.6±1.2	67.7±2.4	C5	28.4±1.2	36.4±1.0	38.9±2.3
Z18	22.9±2.1	32.9±2.5	38.3±2.0	NNM^b	59.7±0.7	65.4±2.4	84.1±1.3

	Compd.	R¹	R²	Regression equation	r	EC₅₀/(μg•mL^–1)
Curative	Z5	4-Br	Br	y=0.9764x+2.7880	0.9798	184.3
	Z12	4-OCH₃	F	y=0.8768x+3.2688	0.9961	94.3
	Z20	4-Br	OCH₃	y=0.9034x+2.9644	0.9973	179.2
	NNM^b	—	—	y=0.9338x+2.8199	0.9915	216.1
Protection	Z5	4-Br	Br	y=0.8797x+3.0150	0.9961	180.1
	Z7	4-OCH₃	CH₃	y=0.8934x+3.0322	0.9779	159.4
	Z12	4-OCH₃	F	y=0.7942x+3.4156	0.9902	98.8
	NNM	—	—	y=1.0142x+2.6898	0.9928	189.6

	Compd.	R¹	R²	Regression equation	r	EC₅₀/(μg•mL^–1)
Curative	Z5	4-Br	Br	y=0.9764x+2.7880	0.9798	184.3
	Z12	4-OCH₃	F	y=0.8768x+3.2688	0.9961	94.3
	Z20	4-Br	OCH₃	y=0.9034x+2.9644	0.9973	179.2
	NNM^b	—	—	y=0.9338x+2.8199	0.9915	216.1
Protection	Z5	4-Br	Br	y=0.8797x+3.0150	0.9961	180.1
	Z7	4-OCH₃	CH₃	y=0.8934x+3.0322	0.9779	159.4
	Z12	4-OCH₃	F	y=0.7942x+3.4156	0.9902	98.8
	NNM	—	—	y=1.0142x+2.6898	0.9928	189.6

Compd.	Xac		Psa		Xoo
Compd.	100 µg/mL	50 µg/mL	100 µg/mL	50 µg/mL	100 µg/mL	50 µg/mL
Z1	25.1±1.1	21.2±1.2	35.4±2.4	22.7±2.2	25.4±2.4	12.7±0.5
Z2	38.2±0.8	23.5±0.8	47.9±2.0	34.7±2.7	27.9±2.0	14.7±2.7
Z3	23.9±5.4	18.4±0.9	52.9±4.8	44.9±2.3	32.9±4.8	10.9±2.3
Z4	22.9±0.5	21.7±5.7	50.5±2.4	39.9±2.5	30.5±2.4	19.9±2.5
Z5	43.5±2.7	31.3±1.7	25.4±5.4	12.7±1.2	45.4±1.4	22.7±1.2
Z6	30.1±1.6	27.1±2.4	37.9±2.0	24.7±2.7	27.9±2.0	14.7±2.7
Z7	24.5±1.2	12.4±8.2	61.8±5.7	44.5±3.6	11.8±2.7	—
Z8	38.5±1.9	22.4±2.3	38.8±3.5	24.0±5.6	28.8±3.5	14.0±0.6
Z9	36.7±1.8	33.6±0.8	28.0±2.6	11.2±3.0	28.0±2.6	11.2±3.0
Z10	26.0±2.5	15.7±3.8	13.9±3.0	7.5±0.9	33.9±3.0	17.5±3.9
Z11	37.7±1.8	26.4±1.8	27.3±1.1	11.2±4.3	27.3±3.1	11.2±4.3
Z12	45.8±4.9	24.3±1.9	37.5±3.9	22.5±3.9	27.5±3.9	14.5±3.9
Z13	57.8±2.1	35.7±2.1	27.4±4.3	15.1±4.6	27.4±4.3	15.1±2.1
Z14	33.8±1.8	21.9±1.8	49.0±4.2	32.3±1.2	59.0±4.2	32.3±1.2
Z15	32.1±1.6	21.5±1.6	27.2±4.6	15.1±1.2	27.2±4.6	16.1±1.6
Z16	42.6±3.3	21.2±3.5	15.6±4.2	9.1±0.2	35.6±4.2	23.1±1.2
Z17	35.6±1.8	23.1±2.2	36.5±1.0	25.2±2.1	61.5±1.0	45.2±2.1
Z18	33.1±3.8	20.7±0.3	35.4±3.3	28.8±4.3	25.4±3.3	13.8±4.3
Z19	35.7±2.7	15.5±2.5	29.2±4.6	13.2±2.6	29.2±4.6	12.2±4.6
Z20	59.7±2.6	27.3±0.5	32.2±0.8	21.6±0.6	22.2±0.8	11.6±3.6
Z21	21.2±.5	11.1±2.2	25.2±0.6	11.5±1.6	35.2±0.6	17.5±1.6
Z22	23.3±1.4	15.6±1.3	35.8±0.1	21.6±2.1	45.8±0.1	21.6±3.1
Z23	38.9±2.6	27.1±1.5	42.1±1.2	31.0±1.0	32.1±3.2	18.0±2.0
Z24	32.2±3.3	16.7±0.6	36.1±2.3	29.3±5.4	26.1±2.3	19.3±1.4
Z25	57.5±2.7	45.4±0.3	37.2±0.9	27.5±3.2	67.2±0.9	57.2±3.2
TC^b	52.2±0.5	46.1±1.8	52.1±3.4	42.2±3.9	55.4±3.4	42.7±1.2
BT^b	47.7±1.0	33.0±2.6	49.2±3.0	36.3±1.8	50.9±2.0	36.9±2.7

含喹唑啉酮的查尔酮衍生物的设计、合成及生物活性研究