The earliest step in cell division in bacteria is the assembly of FtsZ, an essential cell division protein, into a ring at the division site. FtsZ has GTPase activity and can assemble in vitro to form protein filaments. The present work involved the study of eight phenylpropanoids (cinnamic, p-coumaric, caffeic, chlorogenic, ferulic, 3,4-dimethoxycinnamic and 2,4,5-trimethoxycinnamic acids and eugenol) as inhibitors of Escherichia coli FtsZ. Phenylpropanoids make up the majority of our diet and act as antibacterial agents. Polymerization and GTPase inhibition assays showed that chlorogenic and caffeic acids were the most active amongst these (IC 50 of 70 and 106 mM, respectively). Circular dichroism studies indicated that chlorogenic acid perturbed the protein conformation and electron microscopy showed distorted filaments. Bacillus subtilis 168 cells treated with the phenylpropanoids were longer when compared to the control. The highest binding energy was observed between chlorogenic acid and the homology modelled E. coli FtsZ, which was consistent with the experimental results. A strong negative correlation was observed between binding energy and inhibition of the polymerization ability. 3D-Quantitative structureactivity relationship studies using GTPase activity indicated that the presence of more hydrophilic groups around the 39-and 49-carbon increased the activity. The effect of stress-induced formation of cell filamentation has to be understood before confirming the role of phenylpropanoids as FtsZ inhibitors. INTRODUCTIONAntimicrobial resistance is a global concern due to its increased prevalence. The major issues are the reduced susceptibility to currently available antimicrobial agents and shortage of newly approved compounds. A growing number of Gram-positive (Staphylococcus aureus, Streptococcus pneumoniae, etc.) and Gram-negative (Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, etc.) pathogens are responsible for infection in both the community and health-care settings (Furtado & Nicolau, 2010). Around 19-60 % of Staphylococcus aureus isolates from ocular infections have been shown to be resistant to macrolides, penicillin and fluoroquinolones (McDonald & Blondeau, 2010). The overall levels of antibiotic resistance can be dramatically decreased by focusing on the overuse of antibiotics, the pharmacokinetic and pharmacodynamic properties of different drug formulations, and use of proper hygiene and protective barriers. There is also a need for the introduction of new antimicrobial agents with novel targets.FtsZ is a bacterial cytoskeleton protein which assembles into a protofilament in a GTP-dependent manner. This forms a dynamic Z-ring at the mid-cell position. A study done in E. coli showed that 12 different proteins congregate at the Z-ring in a sequentially dependent pathway, causing assembly of the septal ring that guides the synthesis of the circumferential septum (Buddelmeijer & Beckwith, 2002;Bernhardt & de Boer, 2003;Romberg & Levin, 2003; Schmidt et al., 2004). The septal r...