Quantification and In Silico Toxicity Assessment of Tazarotene and its Impurities for a Quality and Safe Drug Product Development.

Tazarotene is internationally accepted common name for ethyl 6-[(4,4-dimethylthiochroman-6-yl)ethynyl]nicotinate. It is a synthetic retinoid used for the topical treatment of mild to moderate plaque psoriasis, acne vulgaris and photo aging. To ensure the quality of drug product and drug substance, a LC-MS compatible UHPLC method was developed for quantification of drug and its related substances. Stationary phase with fused core particle technology is used for the separation of impurities. Limit of quantification and limit of detection of the method are 0.1 and 0.03%, respectively. Precision of the method for Tazarotene and all its related substances is less than 2.2% RSD. The correlation coefficient is >0.999. Accuracy of method is ranged from 95.3% to 107.0%. Application of this method in stability analysis has been demonstrated by analyzing stressed samples. Experimental design is used for the verification of robustness of the method. To ensure the safety, an in silico toxicity of the drug and its related substances were determined using TOPKAT and DEREK toxicity predictions Both UHPLC and in silico methods were validated as per the ICH Q2 and ICH M7 guidelines, which will enable a rapid product development of Tazarotene topical formulations while ensuring the safety and quality of product.

Synthesis, Characterization, and Biological Activities of Pendant Arm-Pyridyltetrazole Copper(II) Complexes: DNA Binding/Cleavage Activity and Cytotoxic Studies.

2-(1H-Tetrazol-5-yl)pyridine (L) has been reacted separately with Me2NCH2CH2Cl⋅HCl and ClCH2CH2OH to yield two regioisomers in each case, N,N-dimethyl-2-[5-(pyridin-2-yl)-1H-tetrazol-1-yl]ethanamine (L1)/N,N-dimethyl-2-[5-(pyridin-2-yl)-2H-tetrazol-2-yl]ethanamine (L2) and 2-[5-(pyridin-2-yl)-1H-tetrazol-1-yl]ethanol (L3)/2-[5-(pyridin-2-yl)-2H-tetrazol-2-yl]ethanol (L4), respectively. These ligands, L1-L4, have been coordinated with CuCl2 ⋅H2O in 1 : 1 composition to furnish the corresponding complexes 1-4. EPR Spectra of Cu complexes 1 and 3 were characteristic of square planar geometry, with nuclear hyperfine spin 3/2. Single X-ray crystallographic studies of 3 revealed that the Cu center has a square planar structure. DNA binding studies were carried out by UV/VIS absorption; viscosity and thermal denaturation studies revealed that each of these complexes are avid binders of calf thymus DNA. Investigation of nucleolytic cleavage activities of the complexes was carried out on double-stranded pBR322 circular plasmid DNA by using a gel electrophoresis experiment under various conditions, where cleavage of DNA takes place by oxidative free-radical mechanism (OH(⋅)). In vitro anticancer activities of the complexes against MCF-7 (human breast adenocarcinoma) cells revealed that the complexes inhibit the growth of cancer cells. The IC50 values of the complexes showed that Cu complexes exhibit comparable cytotoxic activities compared to the standard drug cisplatin.

Influence of dielectric constant on protonation equilibria of L-aspartic Acid in acetonitrile- and ethylene glycol-water mixtures.

The protonation constants of L-Aspartic acid have been studied pH-metrically in various concentrations (0-60% v/v) of acetonitrile- and ethylene glycol-water mixtures maintaining an ionic strength of 0.16 mol L-1 at 303K. The protonation constants have been calculated with the computer program MINIQUAD75 and are selected based on statistical parameters. Linear variation of step-wise protonation constants (log K) with the reciprocal of the dielectric constant of the solvent mixture has been attributed to the dominance of the electrostatic forces.

Effect of dielectric constant on protonation equlibria of L-dopa and 1, 10 -phenanthroline in dioxan-water mixtures.

Solute-solvent interactions of L-dopa and 1, 10-phenanthroline have been studied in 0-60% v/v dioxan-water media using pH-metric method. The protonation constants have been calculated with the computer program MINIQUAD75. Selection of the best fit chemical model of the protonation equilibria is based on standard deviation in protonation constants and residual analysis using crystallographic R-factor and sum of squares of residuals in all mass balance equations. Linear variation of protonation constants with inverse of dielectric constants of the solvent mixture has been attributed to the dominance of the electrostatic forces. Distribution of species, protonation equilibria and effect of influential parameters on the protonation constants have also been presented.

Chemical speciation of binary complexes of embelin with some biologically important metal ions.

Protonation and complexation equilibria of embelin were investigated in 86% v/v dimethyl sulphoxide - water mixture electrometrically at an ionic strength of 0.17 mol dm-3 and at a temperature of 303K. The best fit chemical models were arrived at based on statistical grounds employing crystallographic R factor, χ2, skewness and kurtosis. The existence of binary complex species with Co(II), Ni(II), Cu(II) and Zn(II) were established from modeling studies using the computer program MINIQUAD75. Distribution diagrams of various species of the complex in relation to pH are presented.

DoD2007: 1082 molecular biology databases.

UNLABELLED: Molecular biology databases are an integral part of biological research. To date, many databases were established with varied options to access associated biological data. Depending on the data being annotated, some are architecturally similar while others are specialized. In order to provide a partial solution to data integration, we report Database of Databases (DoD2007), constructed using html and javascript. The database has a web-based user interface with simple global search, specific database search, keyword help as well as links to abstracts, full-text and database home pages. Majority of data were derived form Nucleic Acids Research database issue and other published resources. The current release includes 15 categories with updated descriptions and links to 1082 databases, of which, 209 are new entries. New databases included in this issue are represented with '+' sign before the name and a '*' symbol provided for those that remained silent. AVAILABILITY: The database is freely available at http://www.progenebio.in/DoD/index.htm.

DoD2006: molecular biology database update.

DoD2006, an updated version of Database of Databases is an online resource maintained collectively by ProGene Biosciences and Department of Inorganic and Analytical Chemistry, Andhra University. It links to all molecular biology databases that appeared in Nucleic Acids Research 2006 database issue. DoD2006 includes 873 databases, of which, 858 are derived from Nucleic Acids Research database issue and 15 are collected from In Silico Biology, Bioinformation journals and Google Scholar search. Each database has a search option, keyword help and a brief description with direct link to the database home page. The database is freely available online at http://www.progenebio.in/DoD/index.htm.

Prospects of second generation artificial intelligence tools in calibration of chemical sensors.

Multivariate data driven calibration models with neural networks (NNs) are developed for binary (Cu++ and Ca++) and quaternary (K+, Ca++, NO3- and Cl-) ion-selective electrode (ISE) data. The response profiles of ISEs with concentrations are non-linear and sub-Nernstian. This task represents function approximation of multi-variate, multi-response, correlated, non-linear data with unknown noise structure i.e. multi-component calibration/prediction in chemometric parlance. Radial distribution function (RBF) and Fuzzy-ARTMAP-NN models implemented in the software packages, TRAJAN and Professional II, are employed for the calibration. The optimum NN models reported are based on residuals in concentration space. Being a data driven information technology, NN does not require a model, prior- or posterior- distribution of data or noise structure. Missing information, spikes or newer trends in different concentration ranges can be modeled through novelty detection. Two simulated data sets generated from mathematical functions are modeled as a function of number of data points and network parameters like number of neurons and nearest neighbors. The success of RBF and Fuzzy-ARTMAP-NNs to develop adequate calibration models for experimental data and function approximation models for more complex simulated data sets ensures AI2 (artificial intelligence, 2nd generation) as a promising technology in quantitation.