Design, synthesis, docking, Hirshfeld surface analysis and DFT calculations of 2-methylxanthen-9-with the FtsZ protein from Staphylococcus aureus

It is of interest to document the design, synthesis, docking, Hirshfeld surface analysis and DFT calculations of 2-methylxanthen-9-with the FtsZ protein (PDB ID: 3VOB) from Staphylococcus aureus for antimicrobial applications. We report the quantitative structure function data in this context.

Discovery of FtsZ inhibitors by virtual screening as antibacterial agents and study of the inhibition mechanism

Inhibition of bacterial cell division is a novel mechanistic action in the development of new antimicrobial agents. The FtsZ protein is an important antimicrobial drug target because of its essential...

Target Based Virtual Screening of New Leads Inhibitor against Bacterial Cell Division Protein FtsZ for the Discovery of Antibacterial Agents

Background: Staphylococus epidermidis coagulase negative and gram positive streptococci have emerged as major nosocomial pathogens associated with the infection of implanted medical devices and dandruff on human scalp. S. epidermidis filamenting temperature-sensitive mutant Z (FtsZ) gene encoded FtsZ protein that assembles at future bacterial cell division site that forms Z-ring structure. FtsZ is a tubulin homolog protein with low sequence similarity; this makes it possible to inhibit bacterial FtsZ protein without affecting the eukaryote cell division. Objective: In the present study, phytochemicals of Cinnamomum zeylanicum, Punica granatum and Glycyrrhiza glabra were virtually screened for their antibacterial activity against Staphylococcus epidermidis cell division protein, FtsZ. Methods: Molecular docking method was used to investigate new lead inhibitor against bacterial cell division protein FtsZ. SwissADME and ProTox tool were used to evaluate the toxicity of the lead molecule. Results: Molecular docking based screening confirmed that among 122 phytochemicals, β- sitosterol and glabrol showed the highest inhibitory activity against FtsZ. SwissADME tool showed β-sitosterol and glabrol as the ideal antibacterial agents. Conclusion: Structure based drug design strategy has been broadly used to optimize antimicrobial activity of small molecule/ligand against large protein receptor of disease, causing pathogens which gives a major breakthrough in pharmaceuticals industries. The molecular docking and SwissADME tool showed that β-sitosterol and glabrol may be developed to be potential topical and sublingual antibacterial agents, respectively.

Comparativein silicoanalysis offtsZgene from different bacteria reveals the preference for core set of codons in coding sequence structuring and secondary structural elements determination

The deluge of sequence information in the recent times provide us with an excellent opportunity to compare organisms on a large genomic scale. In this study we have tried to decipher the variation in the gene organization and structuring of a vital bacterial gene calledftsZwhich codes for an integral component of the bacterial cell division, the FtsZ protein. FtsZ is homologous to tubulin protein and has been found to be ubiquitous in eubacteria. FtsZ is showing increasing promise as a target for antibacterial drug discovery. Our study offtsZprotein from 143 different bacterial species spanning a wider range of morphological and physiological type demonstrates that theftsZgene of about ninety three percent of the organisms involved in our analyses show relatively biased codon usage profile and significant GC deviation from their genomic GC content. We have also detected a tendency among the different organisms to utilize a core set of codons in structuring theftsZcoding sequence. Our meticulous analysis of theftsZgene linked with the corresponding FtsZ protein show that there is a bias towards the use of specific synonymous codons particularly in the helix and strand regions of the multi-domain FtsZ protein. Overall our findings suggest that in an indispensable and vital protein such as FtsZ, there is an inherent tendency to maintain form and structure for optimized performance in spite of the extrinsic variability in coding features.