Ganesh R. Kokil

Pharmacology and chemistry of diabetes mellitus and antidiabetic drugs: a critical review.

Diabetes mellitus, an epidemic metabolic disorders characterized by high blood glucose level associated with various macrovascular and microvascular complications, is one of the main causes of human suffering across the globe. Researchers around the world mainly focused on insulin, insulin analogues, oral hypoglycemic agents and various other complementary and alternate medicines to control the blood glucose levels in diabetes. The present review summarizes the disorders associated with elevation of blood glucose level, biochemical & endocrinological aspects and the current strategies to control. The emphasis has been laid in particular on the new potential biological targets and the possible treatment as well as the current ongoing research status on new generation hypoglycemic agents.

Rheumatoid arthritis: a new challenge in coming era.

Rheumatoid arthritis (RA) is mainly an auto-immune disease characterized by inflammation in joints. 1 in 50 people develop RA at some stage and at any age. This review summarizes the etiology, pathophysiology, risk factor, and treatment related to RA. The emphasis has been laid in particular on the new potential biological targets and the possible treatment as well as the current ongoing research status on RA.

Bioprecursor Prodrugs: Molecular Modification of the Active Principle

A large number of therapeutic medications have undesirable properties that may generate pharmacological, pharmaceutical, or pharmacokinetic barriers in clinical drug applications. Metabolism of drugs by Phase-I & Phase-II metabolic pathways for possibility of active metabolites, which could in turn useful for rational designing of bioprecursor prodrugs of the active principle of interest. This review summarizes various approaches & development of drugs, namely bioprecursor prodrugs and active metabolites related to bioprecursor prodrugs.

QSAR studies of phthalazinones: novel inhibitors of poly (ADP-ribose) polymerase

Over activation of poly (ADP-ribose) polymerase has been involved in the pathogenesis of several diseases including stroke, myocardial infarction, diabetes, shock, neurodegenerative disorder, allergy, and several other inflammatory processes. Owing to the dual response of PARP-1 to DNA damage and its involvement in cell death, pharmacological modulation of PARP-1 activity may constitute a useful tool to increase the activity of DNA-binding antitumor drugs. Quantitative structure activity relationship (QSAR) study vis-à-vis physico-chemical parameters and forward feed neural network analysis for a series of phthalazinone derivatives as potent inhibitors of poly (ADP-ribose) polymerase was performed. The result of QSAR studies obtained allows us to recognize such physico-chemical parameters of phthalazinone derivatives which can be strictly related to the PARP-1 inhibitory activity.

Development and Discovery Avenues in Bioactive Natural Products for Glycemic Novel Therapeutics

Abstract Bioactive natural products are an excellent source of novel therapeutics. The search for bioactive molecules from nature continues to play a major role in developing new generation natural products of therapeutic importance. The present critical review includes research work carried out by active researchers in natural products’ chemistry, pharmacology and therapeutics, and their implications in antidiabetic medications. This compiled scientific information will be a useful resource for future research especially in indentifying promising leads and direction for the development of novel drugs including useful adjuvants for the treatment of diabetic patient. The present therapeutic approaches in the treatment of diabetes are mainly focused to lower the elevated blood glucose by reducing its absorption in gastrointestinal tract, enhancing the sensitivity of insulin, controlling or modulating hepatic glucose output, and increased utilization of the glucose by the peripheral tissues. Involvement of oxidative stress and its impact on the cellular damage in diabetes mellitus has been established and could be a useful paradigm for the development of novel antihyperglycemics along with other therapeutic strategies. The present review also highlights the effects of various herbs, phytoconstituents, phytochemicals, microbial metabolites, and products of marine origins on hyperglycemic/diabetic conditions. Furthermore, efforts were made to discuss novel molecular targets such as insulin-signaling pathways, peroxisome proliferative activating receptor-γ, and G-protein-coupled receptors that are participating in enhancing/influencing insulin secretion, critical carbohydrate metabolism pathways, endoplasmic reticulum stress-related pathways, intracellular events associated intracellular inflammation, and chromatin-modification pathways involvement in antidiabetic activity and their significance.

Self-assembling asymmetric peptide-dendrimer micelles - a platform for effective and versatile in vitro nucleic acid delivery

Despite advancements in the development of high generation cationic-dendrimer systems for delivery of nucleic acid-based therapeutics, commercially available chemical agents suffer from major drawbacks such as cytotoxicity while being laborious and costly to synthesize. To overcome the aforementioned limitations, low-generation cationic peptide asymmetric dendrimers with side arm lipid (cholic and decanoic acid) conjugation were designed, synthesized and systematically screened for their ability to self-assemble into micelles using dynamic light scattering. Cytotoxicity profiling revealed that our entire asymmetric peptide dendrimer library when trialled alone, or as asymmetric dendrimer micelle-nucleic acid complexes, were non-cytotoxic across a broad concentration range. Further, the delivery efficiency of asymmetric peptide dendrimers in H-4-II-E (rat hepatoma), H2K (mdx mouse myoblast), and DAOY (human medulloblastoma) cells demonstrated that cholic acid-conjugated asymmetric dendrimers possess far superior delivery efficiency when compared to the commercial standards, Lipofectamine 2000 or Lipofectin®.