Conformationally Selective 2-Aminotetralin Ligands Targeting the alpha2A- and alpha2C-Adrenergic Receptors.

Many important physiological processes are mediated by alpha2A- and alpha2C-adrenergic receptors (α2Rs), a subtype of class A G protein-coupled receptors (GPCRs). However, α2R signaling is poorly understood, and there are few approved medications targeting these receptors. Drug discovery aimed at α2Rs is complicated by the high degree of binding pocket homology between α2AR and α2CR, which confounds ligand-mediated selective activation or inactivation of signaling associated with a particular subtype.

Evaluation of adverse drug reactions of chemotherapeutic agents used in advanced non-small cell lung cancer - experience from a rural tertiary care institution in North Eastern India.

Background: Lung cancer is one of the major causes of morbidity and mortality both in developed and developing countries. Adverse drug reactions (ADRs) are inevitable, albeit unwanted aspects of cancer chemotherapeutic agents used in lung cancer.

Aim And Objectives: To determine common ADRs and the severity of ADRs of different chemotherapeutic agents used in non-small cell lung cancer (NSCLC) patients.

A new class of 5-HT /5-HT receptor inverse agonists: Synthesis, molecular modeling, in vitro and in vivo pharmacology of novel 2-aminotetralins.

Background And Purpose: The 5-HT receptor subtypes 5-HT and 5-HT are important neurotherapeutic targets, though, obtaining selectivity over 5-HT and H receptors is challenging. Here, we delineated molecular determinants of selective binding to 5-HT and 5-HT receptors for novel 4-phenyl-2-dimethylaminotetralins (4-PATs).

Experimental Approach: We synthesized 42 novel 4-PATs with halogen or aryl moieties at the C(4)-phenyl meta-position.

()-5-(2'-Fluorophenyl)-,-dimethyl-1,2,3,4-tetrahydronaphthalen-2-amine, a Serotonin Receptor Modulator, Possesses Anticonvulsant, Prosocial, and Anxiolytic-like Properties in an Knockout Mouse Model of Fragile X Syndrome and Autism Spectrum Disorder.

Fragile X syndrome (FXS) is a neurodevelopmental disorder characterized by intellectual disabilities and a plethora of neuropsychiatric symptoms. FXS is the leading monogenic cause of autism spectrum disorder (ASD), which is defined clinically by repetitive and/or restrictive patterns of behavior and social communication deficits. Epilepsy and anxiety are also common in FXS and ASD.

Catalytic Asymmetric Epoxidation of Aldehydes with Two VANOL-Derived Chiral Borate Catalysts.

A highly diastereo- and enantioselective method for the epoxidation of aldehydes with α-diazoacetamides has been developed with two different borate ester catalysts of VANOL. Both catalytic systems are general for aromatic, aliphatic, and acetylenic aldehydes, giving high yields and inductions for nearly all cases. One borate ester catalyst has two molecules of VANOL and the other only one VANOL.

Defluoridation using novel chemically treated carbonized bone meal: batch and dynamic performance with scale-up studies.

Novel defluoridating adsorbent was synthesized by chemical treatment of carbonized bone meal using aluminum sulfate and calcium oxide. Precursor for chemical treatment was prepared by partial carbonization of raw bone meal at 550 °C for 4 h. Maximum fluoride removal capacity was 150 mg/g when carbonized bone meal (100 g/L) was treated with aluminum sulfate (500 g/L) and calcium oxide (15 g/L).

Multicomponent Catalytic Asymmetric Synthesis of trans-Aziridines.

A multicomponent trans-aziridination of aldehydes, amines, and diazo compounds with BOROX catalysts is developed. The optimal protocol is slightly different for aryl aldehydes than for aliphatic aldehydes. The key to the success with aryl aldehydes was allowing the catalyst, aldehyde, and amine to react for 20 min before addition of the diazo compound.

Multicomponent cis- and trans-Aziridinatons in the Syntheses of All Four Stereoisomers of Sphinganine.

All four stereoisomers of sphinganine can be synthesized by a multicomponent aziridination of an aldehyde, an amine and an α-diazo carbonyl compound mediated by a BOROX catalyst with high asymmetric induction (≥96% ee). The threo isomers are available from ring-opening of cis-aziridines by an oxygen nucleophile with inversion at the C-3 position and the erythro-isomers are likewise available from trans-aziridines.

Investigation of antifouling and disinfection potential of chitosan coated iron oxide-PAN hollow fiber membrane using Gram-positive and Gram-negative bacteria.

Chitosan coated iron oxide nanoparticles were impregnated into polyacrylonitrile based hollow fiber membrane. The molecular weight cut off was varied in the range of 120 to 145kDa with the concentration of nanoparticles. Incorporation of nanoparticles improved the permeability, mechanical property and hydrophilicity of the membrane.

A socio-economic study along with impact assessment for laterite based technology demonstration for arsenic mitigation.

Arsenic contamination mitigation technologies have been adsorption-based, but the most widely-used and traditionally available adsorbents suffered inherent limitations, including cost infeasibility and problems associated with regeneration and disposal of the spent adsorbent. The present technology is based on indigenously developed activated laterite prepared from the naturally and abundantly available material, and can hence easily be scaled up for community usage and large scale implementation. The total arsenic removal capacity is 32.

Catalyst-Controlled Multicomponent Aziridination of Chiral Aldehydes.

A highly diastereoselective and enantioselective method for the multicomponent aziridination of chiral aldehydes has been developed with BOROX catalysts of the VANOL (3,3'-diphenyl-2,2'-bi-1-naphthol) and VAPOL (2,2'-diphenyl-(4-biphenanthrol)) ligands. Very high to perfect catalyst control is observed with most all substrates examined including aldehydes with chiral centers in the α- and β-positions. High catalyst control was also observed for a number of chiral heterocyclic aldehydes allowing for the preparation of epoxy aziridines, bis(aziridines) and ethylene diaziridines.

Inhibition of the multidrug efflux pump LmrS from Staphylococcus aureus by cumin spice Cuminum cyminum.

Staphylococcus aureus is a serious causative agent of infectious disease. Multidrug-resistant strains like methicillin-resistant S. aureus compromise treatment efficacy, causing significant morbidity and mortality.

Inactivation of Pseudomonas aeruginosa by Chitosan Coated Iron Oxide Nanoparticles.

Background: Pseudomonas aeruginosa is one of the potent opportunistic pathogens associated with respiratory and urinary tract infection. The bacterium owes its pathogenicity due to the intrinsic resistance to antibiotics and disinfectants.

Objective: The present study is focused on the synthesis of antibacterial chitosan coated iron oxide nanoparticles for rapid inactivation of Pseudomonas aeruginosa.

Inactivation of Pseudomonas aeruginosa by chitosan coated iron oxide nanoparticles.

Background: Pseudomonas aeruginosa is one of the potent opportunistic pathogens associated with respiratory and urinary tract infection. The bacterium owes its pathogenicity due to the intrinsic resistance to antibiotics and disinfectants.

Objective: The present study is focused on the synthesis of antibacterial chitosan coated iron oxide nanoparticles for rapid inactivation of Pseudomonas aeruginosa.

Comparative genome analysis of non-toxigenic non-O1 versus toxigenic O1 .

Pathogenic strains of are responsible for endemic and pandemic outbreaks of the disease cholera. The complete toxigenic mechanisms underlying virulence in strains are poorly understood. The hypothesis of this work was that virulent versus non-virulent strains of harbor distinctive genomic elements that encode virulence.

BOROX catalysis: self-assembled amino-BOROX and imino-BOROX chiral Brønsted acids in a five component catalyst assembly/catalytic asymmetric aziridination.

A five-component catalyst assembly/aziridination reaction is described starting from an aldehyde, an amine, ethyl diazoacetate, B(OPh)(3), and a molecule of a vaulted biaryl ligand (VAPOL or VANOL). A remarkable level of chemo-selectivity was observed since, while 10 different products could have resulted from various reactions between the five components, an aziridine was formed in 85% yield and 98% ee and only two other products could be detected in 3% yield. Studies reveal that the first in a sequence of three reactions is an exceedingly rapid amine-induced assembly of an amino-BOROX chiral Brønsted acid species from VAPOL and B(OPh)(3), which is followed by imine formation from the amine and aldehyde and the concomitant formation of an imino-BOROX chiral Brønsted acid and finally the reaction of the imine with ethyl diazoacetate mediated by the imino-BOROX catalyst to give aziridine-2-carboxylic esters with very high diastereo- and enantioselectivity.

Multicomponent catalytic asymmetric aziridination of aldehydes.

The first multicomponent catalytic asymmetric aziridination reaction is developed to give aziridine-2-carboxylic esters with very high diastereo- and enantioselectivity from aromatic and aliphatic aldehydes. This new method pushes the boundary of the aziridination reaction to substrates that failed with preformed imines.

Substrate-induced covalent assembly of a chemzyme and crystallographic characterization of a chemzyme-substrate complex.

A substrate induced covalent assembly of a highly organized chemzyme known to be effective in both catalytic asymmetric aziridination and aza Diels-Alder reactions is described and the information gained from which led to an efficient one-pot aziridination protocol. The crystal structures of two chemzyme-iminium complexes were elucidated by X-ray diffraction analysis that provides critical insights into the binding of the substrates with the chemzyme.

Seeking passe-partout in the catalytic asymmetric aziridination of imines: evolving toward substrate generality for a single chemzyme.

The asymmetric catalytic aziridination reaction (AZ reaction) of imines derived from dianisylmethyl (DAM) amine and tetra-methyldianisylmethyl (MEDAM) amine were examined with boroxinate catalysts prepared from both the VANOL and VAPOL ligands. This included an evaluation of different protocols for the preparation of the catalyst. The AZ reaction of DAM and MEDAM imines prepared from nine different aryl and aliphatic aldehydes were examined.