Potentially active aspirin derivative to release nitric oxide: In-vitro, in-vivo and in-silico approaches.

The series of newer salicylate derivatives incorporating nitroxy functionality were synthesized and evaluated for their potential effect in gastrointestinal (GI) related toxicity produced by aspirin. The synthesized compounds (5a-j) were subjected to %NO (nitric oxide) release study, in-vitro anti-inflammatory potential, % inhibition of carrageenan-induced paw edema and the obtained results were validated by in-silico studies including molecular docking, MD simulations and in-silico ADME (absorption, distribution, metabolism, and elimination) calculations. Compounds 5a (20.86 %) and 5g (18.20 %) displayed the highest percentage of NO release in all the tested compounds. Similarly, 5a and 5h were found to have (77.11 % and 79.53 %) &(78.56 % and 66.10 %) inhibition in carrageenan induced paw edema in animal mode which were relatively higher than ibuprofen (standard used). The obtained results were validated by molecular docking and MD simulations studies. The molecular docking study of 5a and 5h revealed that docking scores were also obtained in very close proximity of -8.35, -9.67 and -8.48 for ibuprofen, 5g and 5h respectively. In MD simulations studies, the calculated lower RMSD (root mean square deviation) values 2.8 Å and 5.6 Å for 5g and 5h, respectively indicated the stability of ligand-protein complexes. Similarly lower RSMF (root mean square fluctuation) values indicated the molecules remained in the active pocket throughout the entire MD simulations run. Further, in-silico ADME calculations were determined and all compounds obey the Lipinski's rule of five and it was predicted that these molecules would be orally active without any serious toxic effect.

Metalloantibiotics: synthesis, characterization and antimicrobial evaluation of bismuth-fluoroquinolone complexes against Helicobacter pylori.

Novel organometallic compounds have been prepared by complexing the fluoroquinolones, norfloxacin, ofloxacin, ciprofloxacin, sparfloxacin, lomefloxacin, pefloxacin and gatifloxacin, with bismuth. The complexes were characterized by UV, IR, atomic absorption spectroscopy, elemental analysis, differential scanning calorimetry, thermogravimetric analysis and mass spectrometry. Their antibacterial potential against Helicobacter pylori and other microorganisms was investigated. These compounds were found to possess strong activity against Helicobacter pylori with a minimum inhibitory concentration of 0.5 mg L-1. They also exhibited moderate activity against Escherichia coli, Staphylococcus aureus, Bacillus pumilus and Staphylococcus epidermidis. These bismuth-fluoroquinolone complexes have the potential to be developed as drugs against H. pylori related ailments.

Studies on the crystal forms of pefloxacin: preparation, characterization, and dissolution profile.

Different crystal forms of pefloxacin were prepared using solvents of varying polarity. X-ray diffractometry (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), infrared absorption spectroscopy (FT-IR), melting point, microcalorimetry and in vitro dissolution rate studies were conducted to investigate various characterstics of different crystalline forms of the pefloxacin. Five different polymorphs of pefloxacin have been identified on the basis of instrumental techniques. The polymorphs differed in their dissolution profile and all of them showed unusual behavior of highest dissolution in the first 15 min. The rate of dissolution went on decreasing and got stabilized to a constant value after 4 h.

Bismuth-norfloxacin complex: synthesis, physicochemical and antimicrobial evaluation.

Norfloxacin is a fluoroquinolone antibacterial agent which is active against various Gram-positive as well as Gram-negative microorganisms. Presence of metal ions considerably alters the activity of fluoroquinolones against potentially susceptible bacteria. As bismuth is known to possess a good antibacterial activity, bismuth complex of norfloxacin was prepared by reacting bismuth citrate with aqueous solution of norfloxacin. The structure of the bismuth-norfloxacin complex (BNC) was confirmed by spectral, chemical and elemental analysis. Antimicrobial studies were carried out using agar diffusion method against Escherichia coli (ATCC 25922), Klebsiella pneumoniae (NTCC 10320), Staphylococcus aureus (ATCC 29213), Bacillus pumilis (NTCC 8241) and Staphylococcus epidermidis (ATCC 12228). The results showed significant increase (p<0.05, Tukeys test) in antibacterial activity of BNC as compared with norfloxacin and physical mixture of norfloxacin and bismuth citrate. This increase in activity is being considered due to increased bioavailability of the metal drug complex. Thus, the use of the BNC may be preferable over norfloxacin alone.