Synthesis, antimycobacterial evaluation, and molecular docking study of 1,2,4-triazole derivatives

Figures & data

Scheme 1. Synthetic routes of the compounds 1–15.

Table 1. Anti-Mtb activity, molecular docking score, and log P of the compounds 1–15.

Compounds	MIC (μg/mL)	Docking score	Log P^a
1	32	124.4	0.29
2	16	115.4	1.55
3	8	115.5	0.48
4	2	135.9	0.21
5	4	135.1	−0.06
6	16	112.9	1.48
7	16	118.2	3.61
8	32	93.9	1.20
9	32	67.1	0.40
10	16	130.8	1.48
11	8	123.8	1.23
12	16	128.1	0.88
13	16	123.5	1.23
14	32	80.0	0.88
15	32	86.3	1.13
Isoniazid	0.25	99.9	−0.64
Pyrazinamide	120	85.3	−1.31

^a Predicted by ChemDraw.

Figure 1. Time-killing curve of compound 4.

Figure 2. Morphological changes of Mtb. (a) Negative control group; (b) treatment with 1 μg/mL compound 4.

Figure 3. Inhibition of Mtb KatG by compounds 4 and 9.

Figure 4. Intracellular ROS production of Mtb that treated with compound 4 and PZA.

Table 2. Cytotoxicity on Vero cells of compound 4.

Compound	IC50 (μg/mL)	SI
4	126.23 ± 2.54	31.56
INH	72.88 ± 1.23	291.2

Figure 5. Molecular docking analysis for compound 4.

Figure 6. Molecular docking analysis for compound 9.

Table 3. The procedures for evaluating catalase activity of Mtb KatG8.

Reagents	Test	Standard	Blank
KatG solution	500 μL	–	–
PBS	–	1500 μL	2500 μL
Samples (INH, RIF, PZA, compounds 4 and 9)	1000 μL	–	–
Mix the tube with vortex and incubate at 25 °C for 30 min, then add hydrogen peroxide:
H2O2	1000 μL	1000 μL	–
Spin the tubes for 10 s and hold at 25 ± 1 °C for 2 min. Then, add 1000 μL of 1.8 M sulphuric acid to stop the reaction. Record the absorbance at the reagent blank at 240 nm.

Liu C-X, Zhao X, Wang L, Yang Z-C. Quinoline derivatives as potential anti-tubercular agents: synthesis, molecular docking and mechanism of action. Microb Pathog. 2022;165:105507.

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