Ch. Sridhar

The application of cationic liposome reagents has advanced DNA and mRNA transfection research in vitro, and data are accumulating which show their utility for in vivo gene transfer. However, chemical structure-activity data leading to a better mechanistic understanding of their biological activity is still limited. Most of the cationic lipid reagents in use today for this application are formulated as liposomes containing two lipid species, a cationic amphiphile and a neutral phospholipid, typically dioleoylphosphatidylethanolamine (DOPE). The studies reported here examine the effects of some systematic chemical structural changes in both of these lipid components. Cationic and neutral phospholipids were formulated together as large multilamellar vesicles (MLV) or small sonicated unilamellar vesicles (SUV) in water, and each formulation was assayed quantitatively in 96-well microtiter plates under 64 different assay conditions using COS.7 cells and an RSV-beta-galactosidase expression plasmid. The cationic lipid molecules used for these studies were derived from a novel series of 2,3-dialkyloxypropyl quaternary ammonium compounds containing a hydroxyalkyl moiety on the quaternary amine. A homologous series of dioleylalkyl (C18:1) compounds containing increasing hydroxyalkyl chain lengths on the quaternary amine were synthesized, formulated with 50 mol % DOPE, and assayed for transfection activity. The order of efficacy was ethyl > propyl > butyl > pentyl > 2,3-dioleyloxypropyl-1-trimethyl ammonium bromide (DOTMA). DOTMA, which is commercially available under the trademark Lipofectin Reagent, lacks a hydroxyalkyl moiety on the quaternary amine. A homologous series of hydroxyethyl quaternary ammonium derivatives with different alkyl chain substitutions were synthesized, formulated with 50 mol % DOPE, and assayed in the transfection assay. The order of transfection efficacy was dimyristyl (di-C14:0) > dioleyl (di-C18:1) > dipalmityl (di-C16:0) > disteryl (di-C18:0). The addition of 100 microM chloroquine in the transfection experiment enhanced the activity of the dioleyl compound by 4-fold and decreased the activity of the dimyristyl compound by 70%. For each of the compounds and formulations examined in this report, large multilamellar vesicles (MLV; diameter 300-700 nm) were more active than small unilamellar vesicles (SUV; diameter 50-100 nm). The neutral phospholipid requirements for transfection activity in COS.7 cells with these cationic lipid molecules were examined.(ABSTRACT TRUNCATED AT 400 WORDS)

Free radicals are well documented for playing a dual role in our body as both deleterious and beneficial species. In low/moderate concentrations free radicals are involved in normal physiological functions but excess production of free radicals or decrease in antioxidant level leads to oxidative stress. It is a harmful process that can be mediates damage to cell structures, including lipids, proteins, RNA and DNA which leads to number of diseases. A variety of synthetic medicine employed in the treatment of different diseases also capable to generate free radicals in body which may causes another disease. The plant sources are rich of antioxidants, phyto-constituents are capable to terminate free radical reactions and prevent our body from oxidative damage. Vegetables and fruits are also important sources of antioxidant substances. Different phytoconstituents and herbal product which are safer then synthetic medicine and beneficial in the treatment of diseases caused by free radicals, it also protect the body by prevent the free radicals to cause tissue injury. Phytoconstituents are conferring less side effect and compatible to body physiology. Therefore it is demand of modern era to use such phytoconstituents or phytomedicines.

Abstract Nanocrystalline ZnO is an effective heterogeneous catalyst for the [2+3]‐cycloaddition of sodium azide with nitriles to afford 5‐substituted 1 H ‐tetrazoles in good yields.