An In-Silico Evaluation of Some Novel Curcumin Derivatives for Antibacterial Activity Against Methicillin Resistant Staphylococcus Aureus.

ABSTRACT

The multiple drug resistance in MRSA (Methicillin resistant Staphylococcus aureus) has become a major clinical problem worldwide. Methicillin resistance (mediated by PBP2a protein) is a serious issue limiting treatment options and necessitating the search of newer safe and effective alternative treatment regimens. Aim of the present study was to evaluate the potential of the plant product ‘Curcumin’ and its derivatives as effective antibacterial agents by means of insilico based studies. Computer aided drug designing is an initial platform helpful to screen novel inhibitors and has tremendous application in the development of new drugs. In the present study a series of 16 derivatives of curcumin were constructed and optimized using chemsketch software.Molecular docking was performed using the GOLD (Genetic Optimization of Ligand Docking) software which is based on genetic algorithm (GA), to study the binding orientation of these derivatives into the PBP2a structure. Derivative 10 (1E,6E)-1,7-bis(3- hydroperoxy-4-hydroxyphenyl)hepta-1,6-diene-3,5-dione) showed best docking fitness value compared to other derivatives(including Curcumin). The molecular, physicochemical, and biological properties were calculated (through molinspiration cheminformatics software) for compounds showing the best docking scores. These compounds were further subjected to toxicity predictions using the Osiris software.