Synthesis, anticandidal activity and cytotoxicity of some tetrazole derivatives

Figures & data

Figure 1. Common structure of azole antifungals.

Scheme 1. The synthetic protocol of the compounds.

Table 1. Some characteristics of the synthesized compounds.

Compounds	R	Yield (%)	Melting point (°C)	Molecular formula	Molecular weight
1	2-Cl	70	85	C10H9ClN4OS	268.5
2	3-CH3	72	79	C11H12N4OS	248
3	3-Cl	75	90	C10H9ClN4OS	268.5
4	3-NO2	80	108	C10H9N5O3S	279
5	4-CH3	81	127	C11H12N4OS	248
6	4-OCH3	88	105	C11H12N4O2S	264
7	4-Cl	90	152	C10H9ClN4OS	268.5
8	4-F	92	137	C10H9FN4OS	252
9	4-Br	94	164	C10H9BrN4OS	313
10	4-NO2	91	135	C10H9N5O3S	279
11	2,4-diCH3	72	142	C12H14N4OS	262
12	2,4-diCl	85	105	C10H8Cl2N4OS	303
13	2,5-diCl	89	80	C10H8Cl2N4OS	303
14	3,4-diCl	88	123	C10H8Cl2N4OS	303

Table 2. Antimicrobial activities of the compounds (µg/mL).

Compounds	A	B	C	D	E	F	G	H
1	24	24	47	47	47	12	47	24
2*	24	12	12	12	60	24	24	12
3	188	188	188	375	47	188	94	94
4	94	188	188	94	47	188	94	188
5	60	32	16	125	60	125	250	60
6^a	30	16	16	30	8	16	32	16
7	60	60	125	125	60	250	125	125
8	60	125	60	125	125	60	250	60
9	125	125	60	250	60	60	250	125
10	60	60	125	250	125	60	30	60
11	188	94	24	188	94	47	94	47
12	60	30	30	60	16	125	125	60
13	60	60	125	60	30	60	125	60
14	24	12	12	94	12	12	24	24
Ref.	30	30	15	3	3	7	15	7

*Compounds 2 and 6 were dissolved in 12 mg/2 mL DMSO and other compounds were dissolved in 24 mg/2 mL DMSO. Ketoconazole: 16 mg/1 mL.

Ref.: Ketoconazole.

A, C albicans (isolate); B, C. albicans (ATCC 90028); C, C. glabrata (isolate-1); D, C. tropicalis (NRRL Y-12968); E, C. krusei (NRRL Y-7179); F, C. parapsilosis (NRRL Y-12696); G, C. albicans (NRRL Y-12983); H, C. glabrata (isolate-2).

Table 3. In vitro cytotoxicity of the compounds.

Compounds	IC50 (µg/mL)*
1	526.6 + 16.06
2	153.3 + 20.8
3	341.6 + 13.92
4	260.8 + 19.29
5	399.3 + 10.4
6	261.4 + 17.33
7	97.44 + 4.46
8	183.9 + 10.31
9	15 + 3
10	80.68 + 11.18
11	260.7 + 17.63
12	407.7 + 28.8
13	455.5 + 23.39
14	131.8 + 13.99

*The values provide the cytotoxicity of the compounds against mouse fibroblast (NIH/3T3) cell line. Incubation was done for 24 h. IC₅₀ is the drug concentration required to inhibit 50% of the cell growth. The values represent mean ± SD of triplicate determinations.