Synthesis, molecular packing and anti-cholinesterase activity of some new C-2 N-substituted anthranilamide derivatives

Abstract

Abstract Synthesis of C-2 N-substituted anthranilamide derivatives was carried out in a straight forward manner, utilizing 2-aminobenzamide and benzyl chloride as starting materials. Their crystal structures have been established by single crystal X-ray crystallographic method. In the molecules of 2-benzylamino-benzamide (3a), intramolecular hydrogen bonding b/w O atom and proton of –NH and classical intermolecular hydrogen bonding of the type N–H · · · O forming eight membered rings in R4 2(8) pattern. In both molecules of 2-(dibenzylamino)benzamide (3b), unlike the molecule in 3a, each H atoms is pointed towards N atom causing intramolecular hydrogen bonding interactions, resulting in S(6) motifs. However, it is interesting to note that both molecules in 3b are lying about inversion centres and form dimers in R4 2(8) motifs; the two dimers are linked via non-classical intermolecular hydrogen bonds C–H · · · O resulting in clusters of four molecules in the structure. In vitro assay results revealed that molecule 3b with IC50 values of 3.8 ± 0.08 μM (AChE) and 17.6 ± 1.10 μM (BChE) possessed better cholinesterase (AChE and BChE) inhibition potential as compared to standard drug galantamine. Preliminary in silico studies showed that more biological active derivatives were also having good pharmacokinetic profile with no AMES toxicity and carcinogenicity.