3D QSAR AND DOCKING STUDY OF INDOLE DERIVATIVES AS SELECTIVE COX-2 INHIBITORS

Objective: Non-steroidal anti-inflammatory agents (NSAIDs) continue to be one of the most widely used groups of therapeutic agents. QSAR (quantitative structure-activity relationship) approach is a very useful and widespread technique for drug design. 3D QSAR facilitates evaluation of three-dimensional molecular fields around molecules and generates a relationship of these fields' values with the activity. Methods: 3D QSAR study was performed on selected twenty-four compounds from synthesized indole derivatives using the stepwise variable selection k-nearest neighbor (kNN) molecular field analysis approach for indicating the contribution of the steric and electronic field for activity. The docking study was performed to further confirm the binding affinity of synthesized molecules (ligands) to COX-2 enzyme as well as to study binding nature. Results: Statistically significant model was generated using VLife Molecular Design Suite 3.5 software with cross-validated correlation coefficient q2 of 0.9461 and high predictive correlation coefficient (Pred_r2) of 0.8782 indicating that the model is robust. The results of docking study suggest that the synthesized compounds have a comparable binding affinity with the COX-2 enzyme. Conclusion: The present study may prove to be helpful in the development and optimization of existing indole derivatives as anti-inflammatory agents with selective COX-2 inhibition

A Comprehensive Review on Floating Drug Delivery System (FDDS)

The main goal of any drug delivery system is to achieve desired concentration of the drug in blood or tissue, which is therapeutically effective and non-toxic for a prolonged period. Current pharmaceutical scenario focuses on the formulation of floating drug delivery system (FDDS). FDDS are low density systems that float over the gastric contents and remain buoyant in the stomach for a prolonged period of time without affecting the gastric emptying rate. The aim of writing this review is to compile the current literature with special focus on the principal mechanism of floatation to attain gastric retention. Effervescent FDDS release CO2 gas, thus reduce the density of the system and remain buoyant in the stomach for a prolonged period of time and released the drug slowly at a desired rate so it can be used to prolong the gastric residence time in order to improve the bioavailability of drug. The review briefly describes the mechanism, types of floating system, advantages, limitation, factors affecting floating system, drug candidates suitable for floating, evaluation parameters and application of the system. These systems are useful to several problems encountered during the development of a pharmaceutical dosage form and the future potential of FDDS. Keywords: Floating drug delivery system, Absorption Window, Effervescent system, floating lag time

Synthesis, Characterization and Evaluation of Analgesic and Anti-inflammatory Activities of Some Novel Indoles

Purpose: Long-term clinical usage of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with significant side effects - gastrointestinal lesions, bleeding and nephrotoxicity. Therefore, the discovery of new safer antiinflammatory drugs represents a challenging goal for this research area. Methods: Various derivatives of 3-(2-aminopyrimidin-4-yl) indoles viz. 4-(4-substitutedphenyl)-6-(2-(4 substitutedphenyl)-1H-indol-3-yl) pyrimidin-2-amine (4a-4r) were synthesized by cyclization of (3-(4- substitutedphenyl)-1-(2-(4-substitutedphenyl)-1H-indol-3-yl) prop-2-en-1-one) of indole with guanidine hydrochloride in the presence of sodium isopropoxide. Their structures were confirmed by FTIR, 1H NMR and elemental analysis. These compounds were investigated for their analgesic, inflammatory and ulcerogenic activities. Results: All the compounds tested (4a-4r) showed analgesic and inflammatory activities. Seven compounds (4d, e, h, j, k, q, p) out of 18 compounds showed antiinflammatory activity comparable to that of the reference standard, indomethacin, but with much lower ulcerogenic action. Compounds 4j and 4k showed 87.4 and 88.2 % inhibition of paw edema, 78.5 and 76.6 % protection against acetic acid-induced writhings and 0.89 and 1.12 of severity index, respectively, compared to 92.7 %, 82.8 % and 2.2, respectively, for indomethacin. Conclusion: The results show that incorporation of an appropriately substituted pyrimidine ring in indole nucleus can afford molecules with good analgesic and anti-inflammatory activities but with reduced gastric irritation

Phytochemical evaluation of the marketed drakshasava formulation by spectroscopic & chromatographic methods

Background: Drakshasava is a general health tonic, carminative and blood purifier. It is used in the treatment of anemia, digestive & cardiac disorders. A review of the literature suggested that modern analytical methods are not reported for the phytochemical evaluation of drakshasava. Objective: To report phytochemical evaluation of Drakshasava Formulation by Spectroscopic & Chromatographic Methods. Materials and methods: Total phenolic, flavonoid, sugar and reducing sugar content in marketed drakshasava formulations were estimated by a UV-Vis spectrophotometer. The markers and extract of drakshasava formulations I & II were scanned by FTIR spectrophotometer individually to find the common bands of the vibrational spectra of markers and formulations. The markers and extract of drakshasava formulations I & II were subjected to HPLC analysis. Results: UV-Vis spectrophotometer analysis revealed that total phenolic, flavonoid, total sugar, & total reducing sugar of marketed drakshasava formulations were within the limit of ayurvedic pharmacopeia. The gradient mobile phase solvent A (HPLC grade water containing 0.85% w/v ortho phosphoric acid) and solvent B (acetonitrile) were optimized by considering the resolution, peak shape, and symmetry. Conclusion: The evaluation parameters reported in this article could be used as a standard reference for quality management of marketed drakshasava formulations

As Review on Microsponge Gel as Topical Drug Delivery System

Microsponges are drug delivery systems composed of porous microspheres. They are little sponge – like spherical particles with an outside surface porous surface. Moreover, they will enhance stability, scale back aspect effect and modify drug unharness favourably. Microsponge technology has several favorable characteristics that make it a flexible drug delivery vehicle. Microsponge  system square measure supported microscopic, chemical compound based mostly microspheres that may suspend or entrap a good type of substances, and might may be incorporated into a developed product like a gel, cream, liquid, powder. The outer surface is often porous, permeating a sustained flow of drugs out of sphere. Microsponges square measure porous, compound microspheres that square measure used principally for typical use and have recently been used for oral administration. microsponge  square measure designed to deliver a pharmaceutical active ingredient with efficiency at the minimum dose and additionally to reinforce solubility, scale back aspect effects and modify drug unharness. Kyewords: Controlled release, drug delivery, care systems, microponges

Synthesis of Thienopyrimidines and their Antipsychotic Activity

A series of thienopyrimidines and related heterocycles were synthesized by refluxing related imidoyl chloride with primary and secondary amines under microwave irradiation and classical heating. The imidoyl chlorides were synthesized from corresponding cyclic imides with phosphorus oxychlorides under microwave irradiation and classical heating. The structures of the compounds were confirmed by FT-IR, NMR. The synthesized compounds were screened for anti psychotic activity

Assessing the efficacy of a tobacco prevention and control intervention in a rural area of India: A quasi-experimental study

Background: Tobacco use, disproportionately higher in rural areas, is a major cause of morbidity and mortality in India. Interventions to reduce tobacco use in rural areas are scarce. Objectives: The objective of this study was to assess the efficacy of a community-directed tobacco prevention intervention in reducing tobacco use in rural areas. Materials and Methods: A single-group pre-/postquasi-experimental study was conducted in Lakhmapur village, Maharashtra. Data were collected from one adult each in 296 and 307 randomly selected village households before and at the end of intervention, respectively. Results: Between pretest and posttest, reported tobacco use reduced from 56.4% to 23.5%; average daily expenditure on tobacco from INR 16.07 to INR 9.47, respectively. A logistic model, controlling for sociodemographic variables, showed that the postintervention group had a significantly lower likelihood of using tobacco; however, males and lower education subgroups were more likely to use. Conclusions: Multipronged community-based interventions involving schools, students, teachers, frontline workers, elected leaders, and community influencers hold promise in reducing tobacco use in rural India

Niosomes: A Novel Carrier Drug Delivery System

Niosomes are a novel drug delivery system, in which the medication is encapsulated in a vesicle. The vesicle is composed of a bilayer of non-ionic surfactants. Niosomes are mostly preferred than liposomes because they are stable and cost effective. Niosomes potentiate the pharmacological action of the drug molecules by delaying the clearance of the drug from the circulation, protecting the drug from biological environment and restricting the effects only to the target cells. In novel drug delivery it has applications on treatment of cancer, used as a carrier in haemoglobin, delivery of the peptide drugs through oral route, in treatment of leishmaniasis, in ophthalmic delivery and as carrier in dermal drug delivery. This review article focuses on the composition, advantages, types of niosomes, methods of preparation, characterization and application of the vesicular system. Keywords: Niosomes, Composition, Types, Method of preparation, Factors affecting, Application

Microsponge as an Emerging Technique in Novel Drug Delivery System

Numbers of developments are implemented in drug delivery system to achieve the goals of optimized efficacy, cost effectiveness of therapy. One of the latest, novel and highly evolving technologies is microsponge drug delivery system which gives controlled release and site specific delivery of active ingredients. They are highly cross linked, porous and polymeric microspheres with size range of 5-300µm. This system is emerging as valuable option for topical delivery of drugs due to characteristics like decreased side effects, improved stability, better formulation flexibility, superior product performance. It is having number of applications in oral, topical, ocular and biopharmaceuticals delivery. The current review describes microsponge technology and details of the formulation methods, evaluation, programmable release mechanisms and applications.   Keywords: Microsponges; Controlled release; Quasi emulsion solvent diffusion; Programmable drug release; Oral administration; Topical drug delivery

Unusually Rapid Response In Psoriasis Treated With PUVA.

Two cases of psoriasis under PUVA therapy presented for its unusual rapid response with quick clearance of lesions within three weeks