Synthesis and potent antistaphylococcal activity of some new 2-[4-(3,4-dimethoxyphenoxy)phenyl]-1,N-disubstituted-1H-benzimidazole-5-carboxamidines

Figures & data

Scheme 1. Synthesis of the 1,N-disubstituted-1H-benzimidazolcarboxamidines 7–11 and 23–33.

Table 1. In vitro antistaphylococcal activity and cytotoxicity results of compound 7–11, 23–33 and their calculated physico-chemical parameters by Lipinski's rule.

	Antistaphylococcal activity			Parameter*
No.	S. aureus (ATTC 25923)	MRSA (ATTC 43300)	Cytotoxicity IC50	a-don	a-acc	Log P	M.Wt.	TPSA
7	>25	>25	NT	1	3	4.03 ± 0.46	346.38	52.08
8	>25	>25	NT	2	5	2.13 ± 0.84	425.46	112.24
9	>25	>25	NT	2	6	2.93 ± 0.91	496.57	101.49
10	>25	>25	NT	1	4	4.54 ± 0.84	418.44	78.38
11	>25	25	NT	2	5	3.70 ± 0.84	390.39	89.38
23	12.5†	12.5	44.4	3	5	2.46 ± 0.84	388.42	101.95
24	12.5	6.25	55.3	3	5	3.48 ± 0.97	430.49	87.96
25	>25	25	15.6	3	5	2.96 ± 0.97	428.48	87.96
26	12.5	6.25	7.3	3	5	4.19 ± 0.97	444.53	87.96
27	12.5	6.25	28.6	3	5	4.54 ± 0.97	458.55	87.96
28	6.25	3.12	35.5	3	5	4.66 ± 0.97	470.56	87.96
29	12.5	6.25	38.8	3	5	4.37 ± 0.97	478.54	87.96
30	>25	>25	NT	3	6	2.75 ± 0.99	459.54	91.20
31	>25	>25	NT	2	5	4.11 ± 1.02	444.52	79.17
32	6.25	6.25	NT	2	5	5.89 ± 1.02	520.62	79.17
33	25	25	NT	2	6	5.17 ± 1.04	549.66	82.41
Ampicillin	0.78	>25	–
Sultamicillin	0.78	25	–
Vancomycin	0.78	0.78	–
Na dodecyl sulfate	–	–	43.8

NT, not tested; MRSA, methicillin resistant Staphylococcus aureus; a-don, the number of H-bond donor; a-acc, the number of H-bond acceptor (Marvin Sketch 6.2.0). Log P calculated lipophilicity (ACD Chemsketch 2012).TPSA, topological polar surface area (Perkin Elmer Chem Draw Pro).

*All calculations were made over the bases of formulas.

†This value was reported as 8 µg/mL in Ref. [5].