Synthesis, characterisation and antitumour activity of some quercetin analogues.

Quercetin is one of the most abundant naturally occurring flavonoid and is associated with a wide range of biological activities, such as antioxidant, antiinflammatory and anticancer activities. However, there are multiple problems associated with the bioavailability of quercetin, thereby restricting its use. Taking this into consideration, the structure of quercetin was modified by removal of multiple hydroxyl groups and introduction of substituents such as Cl, OCH3 and N (CH3)2 on the p-position of the B-ring.

Intermolecular interaction of voriconazole analogues with model membrane by DSC and NMR, and their antifungal activity using NMR based metabolic profiling.

The development of novel antifungal agents with high susceptibility and increased potency can be achieved by increasing their overall lipophilicity. To enhance the lipophilicity of voriconazole, a second generation azole antifungal agent, we have synthesized its carboxylic acid ester analogues, namely p-methoxybenzoate (Vpmb), toluate (Vtol), benzoate (Vbz) and p-nitrobenzoate (Vpnb). The intermolecular interactions of these analogues with model membrane have been investigated using nuclear magnetic resonance (NMR) and differential scanning calorimetric (DSC) techniques.

Study of doxofylline and its degradation products in bulk drug by a newly developed stability-indicating HPLC method.

The purpose of this work was to study the stability behavior of doxofylline under different stress conditions and to develop a sensitive stability-indicating HPLC assay method. The stress conditions applied included heat, moisture, acid-base hydrolysis, oxidation, and UV light. The drug was particularly labile under oxidative and thermal stress conditions, with 58.

Antioxidant and hepatoprotective effect of Garcinia indica fruit rind in ethanol-induced hepatic damage in rodents.

The protective effects of aqueous extracts of the fruit rind of Garcinia indica (GIE) on ethanol-induced hepatotoxicity and the probable mechanisms involved in this protection were investigated in rats. Liver damage was induced in rats by administering ethanol (5 g/kg, 20% w/v p.o.

HPLC method for the determination of emtricitabine and related degradation substances.

A new high-performance liquid chromatography method has been developed for a stability-indicating assay for emtricitabine and the quantification of its related substances. Good resolution between the peaks corresponds to process-related impurities, and degradation products from the analyte were achieved on a C18 HiQSil column using a mobile phase consisting of ammonium formate (pH 4.2) and methanol in a gradient elution mode.

In search of a novel antifungal agent: probing molecular interactions of fluconazole and its analogues with model membranes by NMR and DSC techniques.

Objectives: In search of a novel antifungal agent with high susceptibility and increased antifungal potency it is necessary to increase the overall lipophilicity of these agents. In view of that, we have synthesized different carboxylic acid ester analogues of fluconazole, such as fluconazole-benzoate, fluconazole-p-nitrobenzoate, fluconazole-p-methoxybenzoate and fluconazole-toluate, with varying degrees of lipophilicity. In order to probe molecular level interactions of these molecules with biomembrane, lipid bilayers prepared from l-α-dipalmitoyl phosphatidyl choline (DPPC) as the model membrane were used.

Rational development of neuraminidase inhibitor as novel anti-flu drug.

The highly pathogenic influenza virus has caused many human fatalities and poses an increasing pandemic threat. Neuraminidase inhibitors such as oseltamivir and zanamivir have been widely used in the treatment and have gained remarkable success. Although, they are effective in prevention of influenza; the concern for drug resistance still remains a question.

Tyrosinase inhibitor-loaded microsponge drug delivery system: new approach for hyperpigmentation disorders.

Objective: The aim of the present investigation was to design and formulate appropriate form of glabridin, using microsponge drug delivery system.

Method: Microsponges were prepared by emulsion solvent evaporation method and characterized by drug loading, infrared spectroscopy and scanning electron microscopy. In vitro diffusion studies of gel formulation were performed using ethanol: phosphate buffer (1:1) mixture as receptor medium.

Designing of the mucoadhesive intravaginal spermicidal films.

A mucoadhesive drug delivery system for local delivery of metronidazole through vaginal route was formulated. Films were prepared by solvent evaporation method using various compositions of Carbopol, hydroxypropylmethylcellulose, chitosan, Polyox and propylene glycol. The films were evaluated for their weight, thickness, surface pH, folding endurance, mechanical, drug content uniformity, in vitro drug release, swelling, gelling and mucoadhesion property.

Spacer/Linker based synthesis and biological evaluation of mutual prodrugs as antiinflammatory agents.

Mutual prodrugs of some antiinflammatory agents were synthesized with the aim of improving the therapeutic index through prevention of gastrointestinal complications and to check the efficiency of release of the parent drug in presence of spacer. These mutual prodrugs were synthesized by direct condensation method using dicyclohexyl carbodiimide as a coupling agent and glycine as a spacer. The title compounds were characterized by spectral techniques and the release of the parent drug from mutual prodrug was studied in two different non-enzymatic buffer solutions at pH 1.

In-vitro metabolic inhibition and antifertility effect facilitated by membrane alteration: search for novel antifertility agent using nifedipine analogues.

In search of non-hormonal male contraceptives, analogues of nifedipine, which causes reversible infertility, have been synthesized and their interaction at molecular level with model membrane has been probed. Analogues act differently with respect to their antifertility action. This is achieved by altering the cell metabolism thereby directly affecting the motility which is responsible for fertility.

A simple and precise method for quantitative analysis of lumefantrine by planar chromatography.

A simple, precise and sensitive high performance thin layer chromatographic (HPTLC) method has been developed and validated for drug of choice Lumefantrine in treatment of malaria (P. falciparum). Silica gel 60 F254 HPTLC precoated plates were used for quantitative analytical purpose.

Optimization and establishment of a validated stability-indicating HPLC method for study of the stress degradation behavior of metoprolol succinate.

A stability-indicating HPLC method has been established for analysis of metoprolol succinate in the presence of products generated in a stress degradation study. The drug was subjected to stress conditions of hydrolysis, oxidation, photolysis, and thermal decomposition. Extensive degradation was found to occur in an alkaline medium and under thermal stress.

Search for novel antifungal agents by monitoring fungal metabolites in presence of synthetically designed fluconazole derivatives using NMR spectroscopy.

Resistance to currently available antifungal drugs necessitates development of new drugs using rapid, robust and automated methods to test a large number of newly synthesized drugs in less time. We have compared the effect of ketoconazole, fluconazole and its synthesized analogues on Candida albicans ATCC 10231. A metabolic profile of C.

Search for novel neuraminidase inhibitors: Design, synthesis and interaction of oseltamivir derivatives with model membrane using docking, NMR and DSC methods.

As a part of our ongoing program of developing novel influenza virus inhibitors, some new derivatives of oseltamivir were prepared by modifying the amino group with glycyl, acetyl, benzyl and prolyl moieties. The interactions of these derivatives with neuraminidase have been probed by molecular modeling techniques. Further, the interaction of these derivatives with model membranes prepared from DPPC and the effect on the thermotropic behavior and polymorphism of the bilayers have been investigated by multinuclear NMR and DSC methods.

Antioxidant and antihyperlipidemic activity of Hibiscus sabdariffa Linn. leaves and calyces extracts in rats.

Antioxidant and antihyperlipidemic activities of the extracts of leaves and calyces of Hibiscus sabdariffa were investigated by studying their in vitro inhibitory activity on lipid peroxidation and in vivo effects on cholesterol induced hyperlipidemia. Highest antioxidant activity was exhibited by ethanolic extract of calyces followed by ethanolic extract of leaves followed by aqueous extract of leaves of H. sabdariffa.

Evaluation of immunomodulatory activity of an extract of andrographolides from Andographis paniculata.

The immunomodulatory activity of HN-02, an extract containing a mixture of andrographolides (i.e., andrographolide [88 +/- 5 %] plus 14-deoxyandrographolide and 14-deoxy-11,12-didehydroandrographolide together [12 +/- 3 %]) in a pure powder form was evaluated at 1.

Probing molecular level interaction of oseltamivir with H5N1-NA and model membranes by molecular docking, multinuclear NMR and DSC methods.

Structure-based drug design has led to the introduction of three drugs--oseltamivir (GS-4104), zanamivir (GG-167) and peramivir (RWJ-270201) which target the enzyme neuraminidase, for treatment of influenza infections. Using comparative docking studies we propose that more potent molecules against neuraminidase can be obtained by appending extra positively charged substituents at the C5 position of the oseltamivir skeleton. This provides an additional interaction with the enzyme and may overcome the problem of resistance encountered with these drugs.

Preparation, relative toxicity, chemotherapeutic activity, and pharmacokinetics of liposomal SJA-95: a new polyene macrolide antibiotic.

The research work was designed to compare the relative toxicity, chemotherapeutic activity, and pharmacokinetic parameters of liposomal incorporated SJA-95 with that of free SJA-95, with an objective to reduce toxicity and improve therapeutic activity in vivo. Liposomal-incorporated SJA-95 (Lip SJA-95), prepared using the proliposome method, was found to exhibit a higher LD(50) value in mice, and the relative toxicity was about 2.5 times lower than that of the free drug.

Chemotherapeutic activity of liposomal SJA-95: a new polyene macrolide antibiotic in experimental aspergillosis and cryptococcosis.

The incidence of systemic fungal infections that has risen dramatically over the past three decades has propelled a continuous need for more potent antifungal drugs. The purpose of this research was to evaluate the chemotherapeutic activity of a new heptaene polyene macrolide antibiotic (SJA-95) and liposomal incorporated SJA-95 (lip. SJA-95) in a mouse model of aspergillosis and cryptococcosis respectively.

Cardioprotective activity of Ginkgo biloba Phytosomes in isoproterenol-induced myocardial necrosis in rats: a biochemical and histoarchitectural evaluation.

The protective effects of Ginkgo biloba Phytosomes (GBP) in isoproterenol (ISO)-induced cardiotoxicity and the antioxidant activity involved in this protection were investigated in rats. Myocardial infarction was produced in rats with 65, 85, 120 and 200mg/kg of ISO administered subcutaneously (sc) twice at an interval of 24h. An ISO dose of 85mg/kg was selected for the present study as this dose offered significant alteration in biochemical parameters and moderate necrosis in heart.

Polyamines: Potential anti-inflammatory agents and their possible mechanism of action.

Objective: To evaluate the anti-inflammatory activity of exogenously administered polyamines on experimentally induced acute and chronic inflammation in wistar rats and to elucidate their possible mechanism of action.

Materials And Methods: The in vivo anti-inflammatory activity of polyamines was studied using acute (carrageenin paw edema), sub-acute (cotton pellet granuloma) and chronic (Freund's adjuvant induced arthritis) models of inflammation. The biochemical parameters like liver lipid peroxides, SGOT and SGPT were also measured.

Protein and Peptide drug delivery: oral approaches.

Till recent, injections remained the most common means for administering therapeutic proteins and peptides because of their poor oral bioavailability. However, oral route would be preferred to any other route because of its high levels of patient acceptance and long term compliance, which increases the therapeutic value of the drug. Designing and formulating a polypeptide drug delivery through the gastro intestinal tract has been a persistent challenge because of their unfavorable physicochemical properties, which includes enzymatic degradation, poor membrane permeability and large molecular size.

Homogenization technique for analysis of post-iontophoretic acyclovir content in porcine skin.

The aim of present paper is to develop a method of analysis of acyclovir in porcine skin after iontophoretic delivery using a novel homogenization technique. There are various reported methods available for the analysis of acyclovir in skin samples. All of these methods involve assumption of complete absorption of spiked drug by skin slices for validation.

Probable Mechanism(s) of Antifungal Activity of SJA-95, a Heptaene Polyene Antibiotic.

A new strain, streptomyces sp. S. 24 was isolated from a soil sample collected from Japan.