Owing to essential role in bacterial survival, DNA gyrase has been exploited as a validated drug target.However, rapidly emerging resistance to gyrase-targeted drugs such as widely utilized fluoroquinolones reveals the necessity to develop novel compounds with new mechanism of actions against this enzyme. Here, an attempt has been made to identify new drug-like molecules for Shigella flexneri DNA gyrase inhibition throughin silico approaches. The structural similarity search was carried out using the natural product simocyclinone D8, a unique gyrase inhibitor, to virtually screen ZINC database. A total of 11830 retrieved hits were further screened for selection of high-affinity compounds by implementing molecular docking followed by investigation of druggability according to Lipinski's rule, biological activity and physiochemical properties. Among the hits initially identified, three molecules were then confirmed to have reasonable gyrase-binding affinity and to follow Lipinski's rule. Based on these in silico findings, three compounds with different chemical structures from previously identified gyrase inhibitors were proposed as potential candidates for the treatment of fluoroquinolone-resistant strains and deserve further investigations.

Introduction: Inflammation is basically caused through the conversion of Arachidonic acid into Prostaglandin H2 by CycloOxygenase. In this study, a new algorithmic procedure is applied in order to screen molecules, not only with high affinity to COX-2, but also different from their ancestor compounds. Materials and Methods: NSAIDs, COX-1 and COX-2 molecules were acquired from Drug Bank and Protein Data Bank. Drugs were docked with both proteins, using FlexX software. Top 10 molecules with lowest COX-2 interaction energies and highest differences between COX-2 and COX-1 IEs were selected for structural similarity searches in PUBCHEM and ENCANCED NCI databases. Second generation molecules were docked with proteins once again. Compounds with lower IEs than parents were collected. Bioactivities and bio-availabilities of compounds were analyzed through PASS software and Lipinski rules. A best multi linear regression model was developed based on some physicochemical descriptors for further studies. Results: Fifty NSAIDs were selected and 2000 similar molecules were gathered. Screening the molecules based on Lipinski rules, bioactivities and drug likenesses, a trustable BMLR model was developed with more than 80% accuracy including following descriptors: Log P, Log D, Molar Refractivity, Polarity Number, and Aromaticity Ratio. Finally, 6 compounds were selected as best structurally new compounds for further in vitro analysis. Conclusion: The final molecules, being highly drug-like with affinity and structurally different from their ancestors, can be used in order to develop new lead compounds with higher selectivity.

The field of immune based therapeutics for treatment of common chronic illnesses has exploded leading to significant improvement in the disease processes but a downstream impact on infections. Janus kinase (JAK) inhibitors and Bruton Tyrosine kinase (BTK) inhibitors are becoming more widely used in treatment of chronic inflammatory diseases and chronic leukemias because of simplicity of oral administration. As such, many patients will have improvement in their underlying illnesses and will have greater flexibility to travel. Thus, it is important for travel medicine practitioners to be aware of these agents, their adverse effects and impact on drug interactions and immunizations.