Molecular dynamics simulation of entecavir-silver nanoparticles at different biological pH.

Entecavir is a well-known antiviral drug, commonly prescribed for the treatment of hepatitis B and showed promising therapeutic effects against HBV polymerase. The replication of Hepatitis B Virus requires HBV-DNA polymerase and its natural substrate is deoxyguanosine triphosphate. Entercavir inhibit its activity by phosphorylating into its active metabolite. Furthermore, the efficiency of silver nanoparticles as an antimicrobial or antiviral agent is known for centuries. This study focused on the in-silico stability studies of silver nanoparticles of entecavir. The silver nanoparticles of entecavir synthesized by previously reported method. The stability of drug metal complex was predicted by analysis of variations in internal energies including potential energy, kinetic energy and different non-bonded energies during the simulation run of 4000 picoseconds of different molecular systems. After the simulation run it was concluded that the molecular systems of drug metal complex in aqueous solution at pH 4 showed greater instability as compared to the pH 2 and 6.9. This research gives the idea about the significance of molecular dynamics simulation technique in the field of pharmaceutical sciences for the analysis and characterization of pharmaceutical products and visualizes the effects of different environmental parameters on the structure and physicochemical properties of drug molecules.

Synthesis, characterization and assessment of antioxidant and antibacterial potential of dihydroquinoline-3-carboxylic acid and their metal derivatives.

Metal complexes of drug are used to inhibit growth of pathogenic microorganisms and reduces drug resistance. Moxifloxacin is a dihydroquinoline-3-carboxylic acid 4th generation fluoroquinolone antibiotic that has tendency to bind with metal ions. In current study four moxifloxacin-metal complexes i.e. Moxifloxacin-sliver (Moxi-Ag), Moxifloxacin-rhodium (Moxi-Rh), Moxifloxacin-titanium (Moxi-Ti) and Moxifloxacin-rubidium (Moxi-Rb) have been synthesized and evaluated for antibacterial activities against resistant microorganisms along with antioxidant effects. The structure elucidation was carried out using FTIR, 1H- NMR and UV-Vis spectroscopy. Agar well diffusion method and DPPH (1, 1- dipheny1-2-picrylhydrazyl) methods were used to study the antibacterial and antioxidant activity respectively. Both 1H NMR and FTIR spectra clearly showed that Moxi-metal complexes are formed due to change in their carboxyl stretching band in IR, H-2 and H-5 peak position in 1H NMR. All the Moxi-metal complexes showed distinguished antibacterial effects against both Gram-negative and Gram-positive bacteria as compared to drug which was found resistant against many microorganisms. Moxi-Rb and Moxi-Ag metal complexes showed higher antioxidant activity (IC50 values range from 8.26 - 9.19 µg/ml) than Moxi-Ti and Moxi-Rh metal complexes (IC50 range from 11.23 - 14.65 µg/ml).