ABSTRACT
The manuscript pertains to the synthesis and in vitro cytotoxic evaluation of a series of N-alkylbromo and N-alkylphthalimido-isatins against four different human cancer cell lines namely Colon: HCT-15; Liver: Hep-2; Lung: A-549 and Leukemia: THP-1 at 10 and 100 µM concentrations. The active compounds based on preliminary studies were evaluated for their IC(50) value against six cell lines viz. Colo-205, HCT-15 (Colon), THP-1 (Leukemia), A-549 (Lung), PC-3 (Prostate) and HeLa (Cervix). The active analogue IS-4 exhibited IC(50) values of 4.57, 10.90, 11.75, 12.40 and 54.20 µM against HeLa, PC-3, HCT-15, THP-1 and Colo-205, respectively.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/toxicity , Isatin/chemical synthesis , Isatin/toxicity , Antineoplastic Agents/chemistry , Bromine/chemistry , Cell Line, Tumor , Cell Survival/drug effects , HeLa Cells , Humans , Inhibitory Concentration 50 , Isatin/chemistry , Molecular Structure , Phthalimides/chemistryABSTRACT
Some novel substituted azetidin-2-ones (5-8) were synthesized via [2 + 2] cycloaddition reactions of imines and ketenes and evaluated for their ability to prevent diet and diabetes induced hypercholesterolemia. The test compounds 5a and 7a significantly (p < 0.01) inhibited the rise in serum total cholesterol induced by peanut oil (5.5%), cholesterol (1.5%) and cholic acid (0.5%) diet in both acute and chronic models in a dose dependent manner. Compound 5a also raised the high density lipoprotein-cholesterol levels in chronic diet models by peanut oil (5.5%), cholesterol (1.5%) and cholic acid (0.5%). In a diabetes induced model of hypercholesterolemia, the test compounds were evaluated for preventing diabetes-induced hypercholesterolemia (protocol 1) as well as for lowering post diabetic hypercholesterolemia (protocol 2). Test compounds 5a-g and 7a-d significantly (p < 0.05) reduced serum total cholesterol with a greater reduction in protocol 1 as compared with protocol 2. Based on SAR studies, the substituents that favor hypocholesterolemic activity around the azetidin-2-one nucleus are discussed and a possible mechanism of action is proposed on the basis of their differential effects in two protocols of diabetes-induced hypercholesterolemia.
Subject(s)
Anticholesteremic Agents/chemical synthesis , Anticholesteremic Agents/pharmacology , Azetidines/chemical synthesis , Azetidines/pharmacology , Diabetes Mellitus, Experimental/blood , Diet , Hypercholesterolemia/drug therapy , Animals , Female , Hypercholesterolemia/etiology , Liver/drug effects , Liver/enzymology , Male , Rats , Rats, Wistar , Sterol O-Acyltransferase/metabolism , Structure-Activity RelationshipABSTRACT
A systematic approach through computer assisted design to identify novel quinazolines having anxiolytic and GABAergic activity has been reported.
Subject(s)
Anti-Anxiety Agents/chemistry , GABA Agents/chemistry , Quinazolines/chemistry , Animals , Anti-Anxiety Agents/pharmacology , Dose-Response Relationship, Drug , GABA Agents/pharmacology , GABA Agonists/chemistry , GABA Agonists/pharmacology , GABA-A Receptor Agonists , Maze Learning/drug effects , Maze Learning/physiology , Mice , Quinazolines/pharmacology , Receptors, GABA-A/physiologyABSTRACT
[reaction: see text] Ab initio and density functional studies (DFT) on cycloaddition reactions of 1,3-diazabuta-1,3-dienes with ketenes are reported. The vinylic (C=C) and the carbonyl (C=O) units of the ketenes are found to participate in concerted asynchronous [4 + 2] cycloaddition reactions. The transition states (3t, 4t, and 7t) for these paths have been located on the PE surface at the correlated levels of ab initio calculations. A reasonable mechanism for the formation of [4 + 2] and [2 + 2] adducts is presented.
ABSTRACT
We have used atomistic molecular-dynamics simulations to model the detailed molecular configuration of 5CB (4-n-pentyl-4'-cyanobiphenyl) molecules in the form of a nanoscopic liquid crystal droplet in a vacuum microgravity environment. We find the equilibrium state of droplets consisting of as few as 26 or 50 molecules to exhibit significant nematic ordering. The shape of the droplets is also anisotropic, but there is little angular correlation between the nematic director and the long axis of the droplet. Some tendency to micelle formation is observed in droplets of 50 molecules.
ABSTRACT
Static light scattering and electric field-induced Kerr measurements were performed above the nematic-isotropic phase transition of a terminal-lateral-lateral-terminal negative Poisson ratio trimer. For both measurements the inverse susceptibility was observed to be nearly linear with temperature, a result inconsistent with our previously reported Kerr data [Phys. Rev. E 58, 2041 (1998)].
