Synthesis, antimicrobial and antiviral activity of substituted benzimidazoles

Figures & data

Table 1.  Physicochemical characteristics of synthesized benzimidazole derivatives.

Compound	R1	R2	R3	R4	R5	X	Mol. formula	Mol. wt.	Mp (°C)	Rf	% yield
1	NO2	H	H	H	H	4-NO2	C20H12N4O5	388.33	154–156	0.10*	52.73
2	COOH	H	H	H	H	4-NO2	C21H13N4O5	387.35	209–211	0.48*	14.09
3	H	H	OH	H	H	4-NO2	C20H13N3O4	359.34	229–231	0.47*	16.07
4	OCH3	H	H	H	H	4-NO2	C21H15N3O4	373.36	149–151	0.35*	56.72
5	H	H	Cl	H	H	4-NO2	C20H12N3O3Cl	377.78	219–221	0.90*	41.56
6	H	H	NO2	H	H	4-NO2	C20H12N4O5	388.33	139–141	0.12*	45.54
7	H	H	H	H	H	4-NO2	C20H12N3O3	343.34	199–201	0.70*	39.80
8	H	NO2	H	H	H	4-NO2	C20H12N4O5	388.33	209–211	0.90*	48.65
9	H	Cl	H	H	H	4-NO2	C20H12N3O3Cl	377.78	229–231	0.55*	43.98
10	Cl	H	H	H	H	4-NO2	C20H12N3O3Cl	377.78	219–221	0.83*	38.65
11	H	H	NO2	H	H	2-Br	C20H12Br N3O3	422.23	149–151	0.21*	34.23
12	H	H	OH	H	H	2-Br	C20H13Br N2O2	393.23	149–151	0.16*	47.65
13	COOH	H	H	H	H	2-Br	C21H13BrN2O3	421.24	139–141	0.28*	57.68
14	NO2	H	H	H	H	2-Br	C20H12BrN3O3	422.23	129–131	0.60**	47.39
15	Cl	H	H	H	H	-	C19H12N3OCl	333.83	84–86	0.95**	39.13
16	H	H	Cl	H	H	-	C19H12N3OCl	333.83	224–226	0.48**	47.82
17	H	Cl	H	H	H	-	C19H12N3OCl	333.83	149–151	0.59**	73.91
18	H	H	OH	H	H	-	C19H13N3O2	315.37	64–66	0.15**	11.20
19	H	H	NO2	H	H	-	C19H12N4O3	344.30	244–246	0.22**	48.59
20	H	NO2	H	H	H	-	C19H12N4O3	344.30	239–241	0.31**	70.09
21	NO2	H	H	H	H	-	C19H12N4O3	344.30	49–51	0.90**	14.95
22	COOH	H	H	H	H	-	C20H13N3O3	343.41	139–141	0.13**	45.08
23	OCH3	H	H	H	H	-	C20H15N3O2	329.39	99–101	0.90**	14.20

*Benzene (care-carcinogenic). **Toluene:Chloroform (7:3)

^aReported in Sharma D, Narasimhan B, Kumar P, Jalbout A, Eur. J. Med. Chem. 2008 (In Press)

Scheme 1.  Synthetic scheme for the synthesis of substituted benzimidazole derivatives.

Table 2.  Antimicrobial activity (MIC) of synthesized benzimidazole derivatives.

Compound	Minimum Inhibitory Concentration ( 1 × 10^−3μM/mL)
	S. aureus	B. subtilis	E. coli	A. niger	C. albicans
1	36	18	36	18	36
2	33	266	33	16	33
3	35	35	35	17	35
4	33	33	33	33	8
5	17	33	33	17	4
6	36	36	36	18	9
7	146	146	146	18	9
8	18	18	295	18	18
9	17	33	17	33	17
10	33	33	33	17	17
11	15	15	15	15	7
12	32	32	32	32	4
13	15	30	15	15	30
14	30	30	30	30	15
Std	2*	2*	2*	1**	1**

*Norfloxacin **Fluconazole

Table 3.  MBC and MFC values of synthesized benzimidazole derivatives.

Compound	Minimum Bactericidal/fungicidal Concentration (1 × 10^−3 μM/mL)
	S. aureus	B. subtilis	E. coli	A. niger	C. albicans
1	133	66	133	266	295
2	266	-	266	139	133
3	278	278	278	17	69
4	267	267	267	133	33
5	132	264	264	132	17
6	296	296	296	133	36
7	-	-	-	146	18
8	147	147	-	18	147
9	132	264	132	264	132
10	264	264	264	34	132
11	118	118	118	15	14
12	254	254	254	64	16
13	118	236	118	15	118
14	236	236	236	30	58
Std	19*	19*	19*	40**	40**

*Norfloxacin **Fluconazole

Table 4.  Antiviral activity of synthesized benzimidazole derivatives in HEL cell culture.

Compound	MCC^a (μg/mL)	EC50^b (μg/mL)
		Herpes simplex virus-1 (KOS)	Herpes simplex virus-2 (G)	Vaccinia virus	Vesicular stomatitis virus	Herpes simplex virus-1 TK^− KOS ACV^r
1	>100	>100	>100	>100	>100	>100
2	>100	>100	>100	>100	>100	>100
3	>100	>100	>100	>100	>100	>100
4	>100	>100	>100	>100	>100	>100
5	>100	>100	>100	4	>100	>100
6	>100	100	50	2	45	59
7	100	>20	>20	>20	>20	>20
8	100	>20	>20	10	>20	>20
9	-	-	-	-	-	-
10	>100	>100	>100	>100	>100	>100
11	>100	>100	>100	>100	>100	>100
12	>100	>100	>100	>100	>100	>100
13	>100	>100	>100	>100	>100	>100
14	>100	>100	>100	>100	>100	>100
15	100	>20	>20	>20	>20	>20
16	100	>20	>20	>20	>20	>20
17	>100	>100	>100	>100	>100	>100
18	20	>4	>4	>4	>4	>4
19	>100	>100	>100	>100	>100	>100
20	>100	>100	>100	>100	>100	>100
21	100	>20	>20	>20	>20	>20
22	>100	>100	>100	>100	>100	>100
23	100	>20	>20	>20	>20	>20
Brivudin	>250	0.04	29	5	>250	96
Ribavirin	>250	>250	>250	>250	146	>250
Cidofovir	>250	3	2	7	>250	2
Ganciclovir	>100	0.06	0.06	>100	>100	1

^aRequired to cause a microscopically detectable alteration of normal cell morphology.

^bRequired to reduce virus-induced cytopathogenicity by 50 %.

Table 5.  Antiviral activity of synthesized benzimidazole derivatives in HeLa cell culture.

Compound	MCC^a (μg/mL)	EC50^b (μg/mL)
		Vesicular stomatitis virus	Coxsackie virus B4	Respiratory syncytial virus
1	>100	>100	>100	>100
2	>100	>100	>100	>100
3	>100	>100	10	>100
4	>100	>100	>100	>100
5	100	>20	>20	>20
6	100	>20	>20	>20
7	100	>20	9	>20
8	100	>20	>20	>20
9	-	-	-	-
10	>100	>100	>100	>100
11	>100	>100	>100	>100
12	>100	>100	>100	>100
13	>100	>100	>100	>100
14	>100	>100	>100	>100
15	100	>20	>20	>20
16	>100	>100	>100	>100
17	>100	>100	>100	>100
18	20	>4	>4	>4
19	>100	>100	>100	>100
20	>100	>100	>100	>100
21	100	>20	>20	>20
22	>100	>100	>100	>100
23	20	>4	>4	>4
DS-5000	>100	>100	9	0.8
(S)-DHPA	>250	>250	>250	>250
Ribavirin	>250	29	146	10

^aRequired to cause a microscopically detectable alteration of normal cell morphology.

^bRequired to reduce virus-induced cytopathogenicity by 50 %.

Table 6.  Antiviral activity of synthesized benzimidazole derivatives in Vero cell culture.

Compound	MIC^a (μg/mL)	EC50^b (μg/mL)
		Para-influenza -3 virus	Reovirus -1	Sindbis virus	Coxsackie virus B4	Punta Toro virus
1	>100	>100	>100	>100	>100	>100
2	>100	>100	>100	>100	>100	>100
3	>100	>100	>100	>100	>100	>100
4	>100	>100	>100	>100	>100	>100
5	>100	>100	>100	>100	>100	>100
6	>100	>100	>100	>100	59	100
7	20	>4	>4	>4	>4	>4
8	>100	>100	>100	>100	>100	>100
9	-	-	-	-	-	-
10	>100	>100	>100	>100	>100	>100
11	>100	>100	>100	>100	>100	>100
12	>100	>100	>100	>100	>100	>100
13	>100	>100	>100	>100	>100	>100
14	>100	>100	>100	>100	>100	>100
15	100	>20	>20	>20	>20	>20
16	100	>20	>20	>20	>20	>20
17	>100	>100	>100	>100	>100	>100
18	20	>4	>4	>4	>4	>4
19	>100	>100	>100	>100	>100	>100
20	>100	>100	>100	>100	>100	>100
21	100	>20	>20	>20	>20	>20
22	>100	>100	>100	>100	>100	>100
23	20	>4	>4	>4	>4	>4
DS-5000	>100	>100	>100	59	>100	100
(S)-DHPA	>250	>250	>250	>250	>250	>250
Ribavirin	>250	45	>250	>250	>250	146

^aRequired to cause a microscopically detectable alteration of normal cell morphology.

^bRequired to reduce virus-induced cytopathogenicity by 50 %.