Synergistic antimicrobial activity, MD simulation studies and crystal structure of natural alcohol motif containing novel substituted cinnamates

Abstract

A series of natural alcohols motif containing novel substituted cinnamates were developed and screened against five bacterial strains namely, Enterococcus faecal (E. faecalis), Escherichia coli (E. coli), Bacillus subtilis (B. subtilis), Pseudomonas aeruginosa (P. aeruginosa) and Klebsiella pneumonieae (K. pneumonieae). Among all cinnamates, YS17 was identified with 100% bacterial growth inhibition across the panel, except in E. faecalis with MIC values of 0.25 mg/mL against B. subtilis and P. aeruginosa whereas 0.125, 0.5 and 1 mg/mL against E. coli, K. pneumonieae and E. faecalis, respectively. The growth inhibitory property of YS17 was further validated by disk diffusion, synergistic study and in vitro toxicity assays. Interestingly, YS17 exhibits synergistic effect in combination with the standard drug Ampicillin (AMP). The single crystal structure analysis of YS4 and YS6 was also performed which reconfirmed their proposed structures. Molecular docking visualized significant non-covalent interactions between E. coli MetAP and YS17 and the structural and conformational changes were further analysed using MD simulation studies. Overall, the study provided a suitable core for further synthetic alterations for their optimization as an antibacterial agent.

Communicated by Ramaswamy H. Sarma

Keywords:

• Antibacterial
• cinnamates
• natural alcohols
• E. coli
• MetAP

Disclosure statement

Authors declare that they have no competing financial interest.

Additional information

Funding

MA gratefully acknowledges the financial support in the form of Core Research Grant from Science & Engineering Research Board (SERB), Govt. of India (Project No. CRG/2018/003967). Iram Irfan acknowledges DST for postdoctoral fellowship under women scientist scheme (WOS-A) (File no: SR/WOS-A/CS-116/2018).