Synthesis， Antifungal Activity and Molecular Docking Study of 1，2，4-Triazole Bis-Schiff Base Derivatives

doi:10.19894/j.issn.1000-0518.220128

Chinese Journal of Applied Chemistry ›› 2023, Vol. 40 ›› Issue (1): 116-125.DOI: 10.19894/j.issn.1000-0518.220128

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Synthesis， Antifungal Activity and Molecular Docking Study of 1，2，4-Triazole Bis-Schiff Base Derivatives

Mou-Cui LI, Yang-Ming DONG, Ying-Hui REN(), Hai-Xia MA, Le QI

Schoolof Chemical Engineering，Northwest University，Xi'an Key Laboratory of Special Energy Materials，Xi'an 710069，China

Received:2022-04-12 Accepted:2022-10-08 Published:2023-01-01 Online:2023-01-28
Contact: Ying-Hui REN
About author:nwuryh@163.com
Supported by:
the Provincial Key-point Natural Science Foundation of Shaanxi, China(2016JZ003)

1. .pdf(558KB)

Abstract

Abstract:

In this paper， five compounds （D1-D5） are successfully synthesized from 3，5-diamino-1，2，4-triazole and substituted benzaldehyde. The in vitro antifungal activities of the compounds against Fusarium graminearum are studied by the mycelial growth rate method and molecular docking technology. The results show that， except for compound D3， the activities of the others are superior to that of the control drug fluconazole， and the inhibitory effect of compound D1 is about 1.8 times than that of the control drug， which could be used as the lead compound against Fusarium graminearum. The results of molecular docking are consistent with the biological activity， that is， the lower the docking binding energy， the stronger the activity against Fusarium graminearum， and hydrogen bonding is the key factor to maintain the stable binding between the drug molecule and the receptor protein. In order to overcome the drug resistance of pathogenic bacteria， the antibacterial effect of the most active compounds D1 and D2 with the fluconazole combined system are investigated， and the results exhibit that co-toxicity coefficient （CTC） values are greater than 120， which shows the synergistic effect when the mass ratio of compound D1 and fluconazole is 1∶2， D2 and fluconazole is 1∶1， 1∶1， 1∶2， 1∶4 and 4∶1， so compound D2 is expected to be a promising compound dispensing agent.

Key words: 1, 2, 4-Triazole, Bis-schiff base, Antifungal activity, Synergistic combinations, Molecular docking

CLC Number:

O626

Mou-Cui LI, Yang-Ming DONG, Ying-Hui REN, Hai-Xia MA, Le QI. Synthesis， Antifungal Activity and Molecular Docking Study of 1，2，4-Triazole Bis-Schiff Base Derivatives[J]. Chinese Journal of Applied Chemistry, 2023, 40(1): 116-125.

Figures/Tables 9

References 39

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Compounds	Functional group
Compounds	ν（N—H）	ν（CN）	ν（C—N）	ν（Ar—H）	ν（CC）	ν（N—N）	ν（C—Cl）	ν（CH₃）	ν（O—H）	ν（C—F）
D1	3 098	1 602	1 349	2 934	1 477	1 022	674	—	3 027	—
D2	3 104	1 599	1 348	3 007	1 538	1 031	—	2 971	—	—
D3	2 988	1 595	1 349	2 912	1 493	1 027	—	2 919	3 359	—
D4	3 352	1 615	1 331	3 040	1 441	1 028	—	—	—	1 110
D5	3 125	1 610	1 331	2 959	1 487	1 033	670	—	—	—

Compounds	Functional group
Compounds	ν（N—H）	ν（CN）	ν（C—N）	ν（Ar—H）	ν（CC）	ν（N—N）	ν（C—Cl）	ν（CH₃）	ν（O—H）	ν（C—F）
D1	3 098	1 602	1 349	2 934	1 477	1 022	674	—	3 027	—
D2	3 104	1 599	1 348	3 007	1 538	1 031	—	2 971	—	—
D3	2 988	1 595	1 349	2 912	1 493	1 027	—	2 919	3 359	—
D4	3 352	1 615	1 331	3 040	1 441	1 028	—	—	—	1 110
D5	3 125	1 610	1 331	2 959	1 487	1 033	670	—	—	—

Compounds	Inhibition rate/%				Toxicity equation	R	EC₅₀
Compounds	2 mg/L	4 mg/L	8 mg/L	16 mg/L	Toxicity equation	R	EC₅₀
D1	16.33	19.33	39.67	62.33	y=1.491x+3.429	0.938	11.31
D2	12.22	18.52	35.93	52.96	y=1.412x+3.351	0.985	14.63
D3	9.37	13.45	24.56	43.86	y=1.299x+3.206	0.967	24.28
D4	8.66	15.22	27.46	53.73	y=1.593x+3.078	0.972	16.09
D5	10.80	18.95	34.88	50.00	y=1.414x+3.306	0.997	15.80
SD	3.33	14.00	19.67	44.16	y=1.769x+2.693	0.965	20.13

Compounds	Inhibition rate/%				Toxicity equation	R	EC₅₀
Compounds	2 mg/L	4 mg/L	8 mg/L	16 mg/L	Toxicity equation	R	EC₅₀
D1	16.33	19.33	39.67	62.33	y=1.491x+3.429	0.938	11.31
D2	12.22	18.52	35.93	52.96	y=1.412x+3.351	0.985	14.63
D3	9.37	13.45	24.56	43.86	y=1.299x+3.206	0.967	24.28
D4	8.66	15.22	27.46	53.73	y=1.593x+3.078	0.972	16.09
D5	10.80	18.95	34.88	50.00	y=1.414x+3.306	0.997	15.80
SD	3.33	14.00	19.67	44.16	y=1.769x+2.693	0.965	20.13

Compounds	Mass ratio	Toxicity equation	R	EC₅₀	ATI	TTI	CTC
D1∶SD	1∶0	y=1.491x+3.429	0.938	11.31	—	—	—
	0∶1	y=1.769x+2.693	0.965	20.13	—	—	—
	1∶1	y=1.444x+3.423	0.992	12.17	165.41	138.99	119.00
	1∶2	y=1.150x+3.796	0.958	11.14	180.70	125.99	143.42
	1∶4	y=1.124x+3.751	0.900	12.89	156.17	115.60	135.10
	4∶1	y=1.036x+3.759	0.955	15.78	127.57	162.38	78.56
	2∶1	y=1.463x+3.353	0.999	13.36	150.67	151.98	99.14
D2∶SD	1∶0	y=1.412x+3.351	0.985	14.63	—	—	—
	0∶1	y=1.769x+2.693	0.965	20.13	—	—	—
	1∶1	y=1.622x+3.222	0.976	12.47	161.43	118.80	135.89
	1∶2	y=1.895x+2.919	0.987	12.11	166.23	112.53	147.22
	1∶4	y=1.555x+3.315	0.990	12.54	160.53	105.52	149.30
	4∶1	y=1.445x+3.428	0.999	12.23	164.60	130.07	126.22
	2∶1	y=1.369x+3.423	0.991	14.672	137.22	125.06	109.21

Synthesis， Antifungal Activity and Molecular Docking Study of 1，2，4-Triazole Bis-Schiff Base Derivatives

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Compounds	ΔG/ （kJ·mol^-1）	Ki/ （μmol·L^-1）	ΔG_vdW+ΔG_Hbond+ΔG_desolv/ （kJ·mol^-1）	ΔG_ele/ （kJ·mol^-1）	ΔG_Tor/ （kJ·mol^-1）	Hydrogen bond
D1	-32.30	3.71	-38.74	-1.05	7.49	CYS A：215， SER A：436， HIS A：217， LYS A：406
D2	-32.17	2.30	-36.74	-0.46	4.98	SER A：436
D3	-23.89	65.07	-30.84	-0.54	7.49	-
D4	-28.62	9.63	-35.19	-0.96	7.49	LYS A：221， SER A：436
D5	-28.66	9.60	-32.84	-0.79	4.98	SER A：436， CYS A：215

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