Synthesis, antifungal and antioxidant screening of some novel benzimidazole derivatives

Figures & data

Scheme 1 Synthetic route for the preparation of the compounds.

Table I.  Physical and spectral data for the compounds.

		Formulas
		Calc.	Found
No	Ar	%C %H %N %S	%C %H %N %S	M.p (°C)	Yield (%)	^1H NMR data (ppm)	ES+
4a		C23H18N6OS.1.2H2O 61.64 4.58 18.75 7.15 61.61 4.56 18.74 7.14		164	48	5.07 (s, 2H, -CH2), 7.31-8.04 (m, 13H, aromatic protons), 9.77, 10.37, 10.59 (s, 3H, CONHNHCSNH)	427
4b		C23H17 ClN6OS 59.93 3.71 18.23 6.95 59.65 3.98 18.57 6.99		272	30	5.06 (s, 2H, -CH2), 7.30-8.06 (m, 12H, aromatic protons), 9.61, 9.91, 10.63 (s, 3H, CONHNHCSNH)	461
4c		C23H17 ClN6OS. 0.8 H2O 58.11 3.94 17.67 6.74 58.05 3.91 17.57 6.74		275	25	5.05 (s, 2H, -CH2), 7.16-7.99 (m, 12H, aromatic protons), 10.43, 10.59, 11.20 (s, 3H, CONHNHCSNH)	461
4d		C23H17 FN6OS. 0.5 (CH3)2CHOH 62.01 4.46 17.71 6.75 61.96 4.42 17.74 6.74		190	20	5.05 (s, 2H, -CH2), 7.21-8.01 (m, 12H, aromatic protons), 9.58, 9.94, 10.66 (s, 3H, CONHNHCSNH)	445
4e		C23H17 FN6OS. 1.0 H2O 59.72 4.14 18.17 6.93 59.67 4.10 18.16 6.91		270	34	5.07 (s, 2H, -CH2), 7.26-8.02 (m, 12H, aromatic protons), 9.92, 10.53, 10.76 (s, 3H, CONHNHCSNH)	445
4f		C23H17 FN6OS. 0.2 (CH3)2CHOH 62.09 4.11 18.40 7.02 62.03 4.60 18.43 7.02		257	19	5.04 (s, 2H, -CH2), 7.16-8.03 (m, 12H, aromatic protons), 9.78, 9.89, 10.57 (s, 3H, CONHNHCSNH)	445
4g		C23H17 BrN6OS 54.65 3.39 16.62 6.34 54.72 3.51 16.67 6.43		237	15	5.07 (s, 2H, -CH2), 7.25-8.01 (m, 12H, aromatic protons), 9.81, 9.93, 11.22 (s, 3H, CONHNHCSNH)	505, 507
4h		C23H17 BrN6OS. 1.5 H2O 51.88 3.78 15.78 6.02 51.91 3.50 15.47 6.07		212	32	5.07 (s, 2H, -CH2), 7.31-8.04 (m, 12H, aromatic protons), 9.61, 9.90, 10.63 (s, 3H, CONHNHCSNH), ^13C: 46, 111, 113, 119, 120, 121, 123.1, 123.3, 123.7, 123.9, 127.9, 128.4, 130.6, 130.7, 133.3, 135, 137, 141, 143, 152, 167	505, 507
4ı		C23H17 BrN6OS 54.65 3.39 16.62 6.34 54.68 3.20 16.45 6.78		185	20	5.07 (s, 2H, -CH2), 7.30-8.07 (m, 12H, aromatic protons), 9.79, 9.88, 10.61 (s, 3H, CONHNHCSNH), ^13C:46, 111, 113, 119, 120, 123.3, 123.9, 130, 131, 133, 134, 137, 139, 142, 152, 167	505, 507
5a		C23H16N6S. 0.2H2O 67.03 4.01 20.39 7.78 67.09 3.92 20.28 8.01		249	35	5.88 (s, 2H, -CH2), 7.26-8.05 (m, 13H, aromatic protons), 10.31 (s, 1H, NH), ^13C:43, 111, 113, 118, 119, 120, 122, 123, 124, 129, 130, 133, 134, 136, 140, 143, 151, 155, 165	409
5c		C23H15ClN6S 62.36 3.41 18.97 7.23 62.12 3.71 18.72 7.50		240	17	5.90 (s, 2H, -CH2), 7.00-8.05 (m, 12H, aromatic protons), 10.53 (s, 1H, NH), ^13C: 43, 111, 113, 116, 117, 119, 120, 122, 123, 124, 130, 131, 133, 134, 136, 142, 143, 151, 155, 165	443
5e		C23H15FN6S. 0.5H2O 63.43 3.70 19.29 7.36 63.37 3.71 19.15 7.31		258	13	5.93 (s, 2H, -CH2), 7.21-8.08 (m, 12H, aromatic protons), 10.58 (s, 1H, NH)	427
5f		C23H15FN6S. 0.5H2O 63.43 3.70 19.29 7.36 63.36 3.71 19.10 7.30		273	21	5.87 (s, 2H, -CH2), 7.10-8.05 (m, 12H, aromatic protons), 10.33 (s, 1H, NH)	427
5h		C23H15BrN6S. 0.7H2O		254	10	5.90 (s, 2H, -CH2), 7.13-8.05 (m, 12H, aromatic protons), 10.53 (s, 1H, NH)	487, 489

Table II.  The in vitro antifungal activity of the compounds.

	Growth inhibition zone diameter (mm)*
Compounds	C.albicans	C.krusei
4a	10	12
4b	15	15
4c	12	12
4d	10	9
4e	12	11
4f	10	9
4h	17	11
5a	10	10
5c	11	10
5e	8	13
5f	8	12
5h	11	15
Fluconazole	19	20

*: weak: < 10, moderate:10–17, significant: >17.

Table III.  The in vitro effects of some compounds on liver LP levels^a.

Compounds^b	nmol/mg protein	% of control
4a	13.81 ± 0.62	85
4c	7.80 ± 0.30	48
4d	18.85 ± 0.82	116
4e	6.82 ± 0.25	42
4f	30.23 ± 0.87	186
4h	9.27 ± 0.43	57
Control^c	16.25 ± 1.45	100
BHT	5.68 ± 0.22	35

^aEach value represents the mean ± S.D. of 2-4 independent experiments

^bConcentration in incubation medium, 10^{− 3} M

^cDimethylsulfoxide only, control for all of the tested compounds and BHT.

Table IV.  The in vitro effects of some compounds and caffeine on EROD enzyme activity in the liver^a.

Compounds	EROD pmol/mg per min	% of control
4a	14.89 ± 018	36
4c	0.00 ± 0.00	0.0
4d	31. 21 ± 0.08	75
4e	13.76 ± 0.11	33
4f	15.69 ± 0.18	38
4g	8.01 ± 0.05	19
4h	0.00 ± 0.00	0.0
4ı	4.3 ± 0.02	10
5a	14.53 ± 0.05	35
5c	0.84 ± 0.04	2.0
5h	0.00 ± 0.00	0.0
Control^b	41.53 ± 0.9898	100
Caffeine	6.40 ± 0.36	15

^aEach value represents the mean ± S.D. of 2-4 independent experiments

^bDimethylsulfoxide only, control for all of the tested compounds and caffeine.