Discovery of target based novel pyrrolyl phenoxy derivatives as antimycobacterial agents: an in silico approach.

A new series of pyrrolyl phenoxy derivatives bearing alkoxy linker were synthesized and evaluated for anti-tubercular activity (anti-TB) against Mycobacterium tuberculosis. Molecular modeling, pharmacophore constructed using GALAHAD to produce an effective alignment of data set and evaluated by Pareto ranking. The pharmacophore features were filtered by Surflex-dock study using enoyl ACP reductase from M. tuberculosis, which is one of the key enzymes involved in type II fatty acid biosynthesis pathway of M. tuberculosis. Compound 6a27 showed the H-bond with NAD(+), whereas compound 6a26 showed H-bonds with Tyr158, Thr196, Met199 and NAD(+) that fitted well into the binding pocket of target InhA. The alkoxy linker bridge and acceptor groups with benzene ring were advantageous for anti-TB activity, which merit further investigation.

Hydrolyzed polyacrylamide grafted maize starch based microbeads: application in pH responsive drug delivery.

The present study details the synthesis, characterization and pharmaceutical application of hydrolysed polyacrylamide grafted maize starch (HPam-g-MS) as promising polymeric material for the development of pH responsive microbeads. Different grades of graft copolymer were synthesized by changing the net microwave irradiation time, while keeping all other factors constant. Acute oral toxicity study performed in rodents ensured the bio-safety of graft copolymer for clinical application. Various batches of aceclofenac loaded microbeads were prepared by ionic gelation method using synthesized graft copolymers and evaluated for formulation parameters. FTIR spectroscopy confirmed the chemical compatibility between drug and graft copolymer. Results of in vitro release study (USP type-II) carried out in two different pH media (pH 1.2 acid buffer and pH 7.4 phosphate buffer) showed that release rate of drug from developed microbeads was a function of both: (a) surrounding pH and (b) the matrix composition. The drug release was relatively higher at alkaline pH as compared to acidic pH and this feature is desirable from viewpoint of site specific drug delivery. A direct correlation was observed between percentage grafting and microbeads performance and it presents a scope for further research on application and optimization of HPam-g-MS based microbeads as drug delivery carriers.

Hydrolyzed polyacrylamide grafted carboxymethylxyloglucan based microbeads for pH responsive drug delivery.

The present study investigates the pharmaceutical application of hydrolyzed polyacrylamide grafted carboxymethylxyloglucan (HPam-g-CMXG), as promising polymeric material for the development of pH responsive microbeads. The graft copolymer was synthesized by conventional free radical polymerization method and saponified to enhance its functionality and characterized. An acute oral toxicity study ensured the bio-safety of developed copolymer for clinical application. Various batches of pH responsive spherical microbeads were developed and evaluated for the effect of process parameters on their overall performance. Result of in vitro drug release study (USP Type-II, paddle method) carried out in two different pH media (pH 1.2 and pH 7.4) showed a triphasic drug release pattern in all the formulations. Both the drug release and swelling of microbeads were significantly higher in simulated intestinal (alkaline) pH compared to simulated gastric (acidic) pH and this nature is desirable for targeted drug delivery. A strong correlation was observed between the process parameters and matrix composition and it directly influenced the drug transport mechanism. In conclusion, the hydrolyzed polyacrylamide grafted carboxymethylxyloglucan holds an immense potential to be explored pharmaceutically as new matrix material for the design of targeted drug delivery system.