Abstract: Epibatidine’ is a nicotinic alkaloid’, was first discovered in the skin of neotropical poisonous frog, ‘Epipedobates tricolor’ found in Ecuador. John Daly in 1974 first isolated a trace quantity of this alkaloid by scarifying several frogs. With the evolution of NMR techniques the structure of this alkaloid was reported in 1992. An year after, Nobel Laureate Prof. E.J. Corey, devised first total synthesis for this alkaloid. Since then this molecule is constantly attracting the attention of Epibatidine is an agonist at nicotinic acetylcholine receptor. Pharmacologically it is 200 to 300 times stronger than morphine and do not cause any addition. The frog species ‘Epipedobates tricolor’ is now been declared as endangered and therefore there is special need for easy syntheses to get the alkaloid for biological evaluations and to save these frogs from extinction. We have developed a Wittig Claisen based protocol for the total synthesis of this drug molecule which would help in investigation rest pharmacological activities of this drug. Structure of Epibatidine Molecule and the frog species from which it was isolated.
Abstract: In current study, a nanoemulsion as drug delivery system (NE) of spray dried Boswellia Serrata Extract (BSE) was developed and characterized to compare it in vitro/Ex vivo diffusion with reference formulation. Pseudo-ternary phase diagrams were constructed by phase diagram by aqueous titration method, of which the evaluation method was improved for solubility, Droplet size and transmittance. The formulation of BSE-loaded NE was optimized by a Simplex lattice mixture experimental design. The optimized nanoemulsion formulation, loading with 199.8 mg g-1 BSE total boswellic acids, consisted of Isopropyl Myristate, Tween 80 and Ethanol (2:8:10, w/w) and it remained stable after storing at 40°C, 25°C, 4°C for at least 6 months. When diluted with water, the NE droplet size was 11.25 nm and the zeta potential was 0.223 mV. The spherical droplet shape was confirmed by TEM analysis. Ex vivo skin permeation and in vivo anti-inflammatory study were conducted. About 3.25 fold increase in flux was seen in case of nanoemulsion, nanogel showed 1.45 fold increase in flux as compared to carbopol gel with highest enhancement ratio 4.57 and 1.59 respectively. Our study illustrated potential of developed nanoemulsion as possible alternative to traditional topical formulations.
Abstract: The current scenario of drug discovery and development is facing a model perturbation, despite significant advances in genomics, proteomics, metabolomics, combinatorial chemistry and high through put assays. There is an urgent need of a paradigm shift in approaches to drug discovery. Natural products of Ayurveda offer a vast potential for novel phytomolecules with clinical activity. In India, Ayurveda is availed of by more than 70% of the population. There has been a renaissance in scientific exploration of medicinal plants with therapeutic activity. New methods have been proposed and developed for such exploration. Ayurvedic Pharmacoepidemiology, Observational therapeutics and Reverse Pharmacology paths have led to significant hits, leads and drug candidates for several diseases. The active phyto-molecules will also provide novel scaffolds for medicinal chemists to enhance efficacy and reduce toxicity. Several plants have shown promise Viz. Mucuna pruriens for Parkinson’s disease, Nycthanthes arbor-tritis for malaria and Phyllanthus amarus for hepatitis. This approach of Reverse Pharmacology has also been adopted globally by several groups. A plea is made to look at the therapeutic activity of natural products for a revolution in drug discovery and development.
Abstract: A series of novel 2,4 diamino-s-triazine was designed as potential Mycobacterium tuberculosis (Mtb) Dihydro folate reductase inhibitors. The synthesized compounds were evaluated in whole cells by employing Resazurin Microtitre Plate Assay (REMA) against Mtb H37Rv, using known DHFR inhibitors Methotrexate and Trimethoprim as standard drugs. The most active compound in the whole cell assay was selected for DHFR enzyme assay against the pathogen and human enzymes. The enzyme assay results revealed that this compound is a selective pathogenic DHFR inhibitor, with 13 fold more selectivity than Methotrexate. Thus, these derivatives have provided promising selective Hits/Leads as MTb DHFR inhibitors and can provide valuable information for further design of potent anti-TB drugs.
Abstract: In the present study, we have carried out extensive non-linear Quantitative-Structure Activity Relationship (QSAR) analysis to correlate in vitro anti-malarial activity against multi drug resistant strain of Plasmodium falciparum. Forty-three synthetic prodiginines with different structural features were used for their potential antimalarial activity. Linear, bilinear, biexponential and parabolic equations were developed. These equations were compared to determine the optimum values of descriptors for very useful and easily interpretable descriptors. The optimum values of these descriptors could be helpful in finding and optimizing a good lead compound. Obtained correlations reveal that various factors like lipophilicity, molecular weight and number of bonds have non-linear relation with the anti-malarial activity.
Abstract: Chitosan is one of the most popular materials in the field of drug delivery due to its adhesivity and biodegradability. Different types of Chitosan based drug carriers have been conceived for various administration routes, such as oral, nasal, transdermal, parenteral, vaginal, cervical and rectal due to its biocompatibility and biodegradability. Chitosan Nanoparticles (NPs) have long been studied as carriers for systemic and targeted drug delivery. Considerable research efforts have been directed towards developing safe and efficient Chitosan NPs-based particulate drug delivery systems. The results indicated that chemical modification of Chitosan NPs can improve their targeting and bioavailability. The main objectives of this review are to study the Chitosan NPs, their preparation methods, characteristics and modification and finally to evaluate their potential applications in drug delivery systems.
Abstract: Administered drugs interact with membrane transporters of epithelia, Blood Brain Barrier and other districts influencing their delivery and efficacy. Drugs can also be used as inhibitors of transporters involved in human pathology. Drug-transporter interactions are responsible of off-target effects contributing to toxicity. High Throughput Screening technologies increased the potential applications in therapy or in predicting side effects. These strategies will be helpful in reducing animal experimentation. The identification of transporters important for drug absorption, delivery and side effect production and the best technologies for studying interactions are the main goals in this field. Amino acid transporters are not yet considered in human therapy in spite of their involvement in several pathologies. The function of the amino acid transporters EAAT1, ASCT2, GLYT2, GLYT1, B0AT1, LAT1 and LAT2 is so far well characterized. Some structural data on these transporters have also been obtained by bioinformatics. Interactions of these proteins with several drugs have been well defined at the molecular level. Large scale and, in some cases, high throughput screening of pharmacological compounds make these transporters of particular interest and potential application in human health.
Open Access journal
