Indium triflate catalyzed microwave-assisted alkenylation of methoxyphenols: synthesis of indenes and chromenes.

In(OTf)3 catalyzed microwave-assisted alkenylation of methoxyphenols was investigated. Exclusive formation of either indenes or chromenes was observed depending on the position of the methoxy group on phenol. The structures of 1H-inden-4-ol derivatives (4a-e) and 4H-chromene derivatives (5a-j) were established by NMR ((1)H & (13)C) and high-resolution mass spectra, which were further supported by single crystal X-ray analysis of 4c and 5a.

A repository of protein abundance data of drug metabolizing enzymes and transporters for applications in physiologically based pharmacokinetic (PBPK) modelling and simulation.

Population factors such as age, gender, ethnicity, genotype and disease state can cause inter-individual variability in pharmacokinetic (PK) profile of drugs. Primarily, this variability arises from differences in abundance of drug metabolizing enzymes and transporters (DMET) among individuals and/or groups. Hence, availability of compiled data on abundance of DMET proteins in different populations can be useful for developing physiologically based pharmacokinetic (PBPK) models. The latter are routinely employed for prediction of PK profiles and drug interactions during drug development and in case of special populations, where clinical studies either are not feasible or have ethical concerns. Therefore, the main aim of this work was to develop a repository of literature-reported DMET abundance data in various human tissues, which included compilation of information on sample size, technique(s) involved, and the demographic factors. The collation of literature reported data revealed high inter-laboratory variability in abundance of DMET proteins. We carried out unbiased meta-analysis to obtain weighted mean and percent coefficient of variation (%CV) values. The obtained %CV values were then integrated into a PBPK model to highlight the variability in drug PK in healthy adults, taking lamotrigine as a model drug. The validated PBPK model was extrapolated to predict PK of lamotrigine in paediatric and hepatic impaired populations. This study thus exemplifies importance of the DMET protein abundance database, and use of determined values of weighted mean and %CV after meta-analysis in PBPK modelling for the prediction of PK of drugs in healthy and special populations.

p-Hexafluoroisopropanol phenyl functionalized graphene for QCM based detection of dimethyl methylphosphonate, a simulant of the nerve agent sarin.

The detection of DMMP (dimethyl methylphosphonate, a simulant of nerve agent sarin) was performed by using p-hexafluoroisopropanol phenyl (HFIPP) functionalized graphene (GR) via hydrogen bond interactions. For this, the HFIPP moiety was covalently functionalized on the surface of GR by a diazo reaction. The HFIPP-GR film-modified QCM electrodes were fabricated and their sensing characteristics towards DMMP were investigated. The proposed sensor showed good response towards sensing DMMP vapor at room temperature. In order to see the effect of HFIPP derivatives on DMMP vapor sensing, a comparative study was also conducted with unfunctionalized graphene. The sensitivity and detection limit of the HFIPP-GR sensor against DMMP vapors were 12.24 Hz ppm-1 and 150 ppb respectively. The HFIPP-GR coated sensors showed good selectivity towards sensing DMMP vapors when compared with common organic vapors.

Hybrid Bioactive Heterocycles as Potential Antimicrobial Agents: A Review.

The ever increasing cases of microbial resistance pose a major threat to the scientific community and therefore the need for discovery and development of newer antimicrobial agents with novel mode of action is becoming critical. One of the ways to tackle this herculean problem is to generate hybrid molecules by combining two or more bioactive heterocyclic moieties in a single molecular platform. The review here describes published results of our research group's endeavors towards development of potential new and safe antimicrobial agents with better effectiveness by using the hybrid approach. In the present review article the landscaping of heterocycles like 4-thiazolidinones, benzimidazole and quinoline are described. Compounds displaying two of more fold antimicrobial activity are included in the review.

Design, synthesis and bioevaluation of novel 6-(4-Hydroxypiperidino)naphthalen-2-ol-based potential Selective Estrogen Receptor Modulators for breast cancer.

In a study directed towards development of novel Selective Estrogen Receptor Modulators (SERMs), 1-(4-(2-(dialkylamino)ethoxy)benzyl)-6-(4-hydroxypiperidin-1-yl)-2-naphthol and corresponding aryl methyl ethers were synthesized and bioevaluated against the estrogen-responsive human MCF-7 breast cancer cell line. The phenolic analogs displayed little or no activity, but aryl methyl ether analogs showed significant cytotoxic potency. Also, representative compounds from the aryl methyl ether series showed significant binding and antagonistic activity against ERα. Two representative compounds were also evaluated for in vitro membrane permeability, plasma stability as well as in-vivo toxicity in mice. The compounds displayed well-acceptable drug-like in vitro membrane permeability as well as plasma stability and were well-tolerated in experimental mice at 300 mg/kg dose.