Synthesis, biological screening and molecular modeling studies of novel 3-chloro-4-substituted-1-(2-(1H-benzimidazol-2-yl)phenyl))-azetidin-2-ones

Figures & data

Scheme 1.  Reagents: (a) anthranilic acid, polyphosphoric acid, reflux 4h; (b) H₂SO₄, different aldehydes reflux; (c) 1,4 dioxane, chloroacetic acid, tryethylamine, reflux.

Table 1.  Antimicrobial activity of synthesized compounds 3a-3h

Compound Micro Organism	Minimum Inhibitory Concentration (μM/L)
	B. Substilis	S. Aureus	S. Faecalis	E. Coli	P. Aeruginosa
Ampicillin	2.87	2.29	2.29	2.87	2.87
DMSO	Nil	Nil	Nil	Nil	Nil
3a	3.01	1.340	4.021	3.351	3.01
3b	2.45	2.757	10.355	10.416	5.514
3c	27.57	25.73	19.60	46.56	44.11
3d	3.196	3.196	1.278	2.55	1.278
3e	36.31	14.13	8.033	28.59	8.61
3f	46.59	6.125	8.0334	10.283	10.604
3g	2.691	3.588	7.476	5.980	9.969
3h	58.31	73.20	85.60	65.75	57.69

Figure 1.  Best poses, orientations, hydrogen bond formed, and Van der Waals and charge interactions of synthesized compound 3a with enzyme transpeptidase.

Table 2.  Molecular docking showing binding score of synthesized compounds in to the active site of enzyme transpeptidase.

Ligand	Binding score using GA* dock (Energy in kj/mole)
Ampicillin	−10.11
3a	−11.32
3b	−10.82
3c	−9.37
3d	−14.83
3e	−6.10
3f	−7.01
3g	−12.18
3h	−5.74

*GA dock is genetic algoritham embeded in software MDS V3.5 used for docking.

Table 3.  Physiscal data of synthesized compounds 3a-3h.

Sr	compound	−R	Formula	Melting point°C
1	3a	−H	C22H16ClN3O	276-278
2	3b	−2Cl	C22H15Cl2N3O	154-156
3	3c	−4Cl	C22H15Cl2N3O	202-204
4	3d	−4F	C22H15ClFN3O	109-111
5	3e	−2OH	C22H16ClN3O2	92-94
6	3f	−4OH	C22H16ClN3O2	197-199
7	3g	−4NO2	C22H15ClN4O3	123-125
8	3h	−4OCH3	C23H18ClN3O2	67-69