Evaluating the anti-cancer potential and pharmacological in-sights of Physalis angulata Root Extract as a strong candidate for future research.

The research targeting the prevention of complications through natural constituents, instigated by the cancer has recently drawn much more attention over the globe. The research in this direction also revealed that the use of natural constituents would considered a promising strategy for diminishing the aforementioned disease and its consequences. Because of the easy availability and safe nature, the recent years, natural resources as strong anticancer agents.

Evaluation of a crystallographic surrogate for kallikrein 5 in the discovery of novel inhibitors for Netherton syndrome.

The inhibition of kallikrein 5 (KLK5) has been identified as a potential strategy for treatment of the genetic skin disorder Netherton syndrome, in which loss-of-function mutations in the SPINK5 gene lead to down-regulation of the endogenous inhibitor LEKTI-1 and profound skin-barrier defects with severe allergic manifestations. To aid in the development of a medicine for this target, an X-ray crystallographic system was developed to facilitate fragment-guided chemistry and knowledge-based drug-discovery approaches. Here, the development of a surrogate crystallographic system in place of KLK5, which proved to be challenging to crystallize, is described.

Improving the bioavailability and anticancer effect of the PCA-1/ALKBH3 inhibitor HUHS015 using sodium salt.

Prostate cancer antigen (PCA)-1/AlkB homologue 3 (ALKBH3) has been identified as a clinically significant factor and siRNA of PCA-1 inhibits DU145 proliferation both in vitro and in vivo. HUHS015 ( 1: ), a previous reported PCA-1 small-molecule inhibitor, was also effective without any obvious side-effects or toxicity. The potency of HUHS015, however, is not satisfying.

The gastrin/cholecystokinin-B receptor on prostate cells--a novel target for bifunctional prostate cancer imaging.

The means of identifying prostate carcinoma and its metastases are limited. The contrast agents used in magnetic resonance imaging clinical diagnostics are not taken up into the tumor cells, but only accumulate in the interstitial space of the highly vasculated tumor. We examined the gastrin/cholecystokinin-B receptor as a possible target for prostate-specific detection using the C-terminal seven amino acid sequence of the gastrin peptide hormone.

MAMBAs: a real-time graphics environment for QSAR.

MAMBAs (Multivariate Analysis Methods in Biomechanistic Activity Studies) is an integrated workstation-based graphics program designed for the investigation of quantitative structure activity relationships (QSAR). It combines many of the commonly used statistical techniques with an extensive database of substituent constants, a variety of molecular and substituent property calculations and detailed graphics-based table and graph editors. Graphical representations of standard substituent generation and optimization techniques are also included.

Molecular surface comparison: application to drug design.

An interactive system for the display and manipulation of molecular surface properties is presented. The property at the molecular surface is mapped onto the sphere by gnomonic projection. This representation allows direct comparison of the surface properties of pairs of molecules.

Substituent variation in azabicyclic triazole- and tetrazole-based muscarinic receptor ligands.

The effect of variation of the 1-azabicyclic substituent on the novel 1,2,3-triazol-4-yl-, 1,2,4-triazol-1-yl, tetrazol-5-yl-, and tetrazol-2-yl-based muscarinic receptor ligands has been studied, and the exo-azabicyclic[2.2.1]hept-3-yl substituent was found to give the most potent and efficacious compounds.

Synthesis and muscarinic activities of quinuclidin-3-yltriazole and -tetrazole derivatives.

The synthesis of 15 methyl or unsubstituted 1,2,3-triazoles, 1,2,4-triazoles, and tetrazoles additionally substituted with a 1-azabicyclo[2.2.2]octan-3-yl group is described.

Emerging differences between 5-HT3 receptor antagonists.

A brief review is presented of some recently described 5-HT3 receptor antagonists. These antagonists are primarily targeted for use as anti-emetics. However, evidence is emerging that there are differences in their basic pharmacology.

Comparison of azabicyclic esters and oxadiazoles as ligands for the muscarinic receptor.

The link between the cognitive deficit associated with Alzheimer type dementia and the loss of cholinergic function in the disease provides a basis for examining muscarinic agonists as potential therapeutic agents. This paper describes the design and synthesis of novel azabicyclic methyl esters as ligands for the muscarinic receptor. Replacement of the methyl ester by a 3-methyl-1,2,4-oxadiazole ring produces potent metabolically more stable muscarinic agonists capable of penetrating the central nervous system.

Antihypertensive and haemodynamic properties of the potassium channel activating (-) enantiomer of cromakalim in animal models.

The present studies describe the blood pressure lowering, and some other haemodynamic effects, of the potassium channel activator, BRL 38227 ((-) enantiomer of cromakalim, CAS 94470-67-4) in various animal models. BRL 38227 was a potent antihypertensive agent following oral administration to conscious spontaneously hypertensive rats, SHR, (0.038, 0.

Effects of granisetron and lorazepam, alone and in combination, on psychometric performance.

The effects of granisetron (160 micrograms kg-1 body weight) and lorazepam (2.5 mg) on psychometric performance were investigated in a randomized, single-blind, crossover, placebo controlled study of twelve healthy male volunteers. There was strong evidence that lorazepam impaired psychometric performance.

Variation in the aromatic ring of cromakalim: antihypertensive activity of pyranopyridines and 6-alkyl-2H-1-benzopyrans.

The synthesis and antihypertensive activity in the spontaneously hypertensive rat of two new series of analogues related to cromakalim (1) are described. In the first series, where the benzopyran nucleus has been replaced by a pyranopyridine nucleus, the position of the nitrogen atom has been found to be critical for activity, and the most potent compounds are the pyrano[3,2-c]pyridines. In the second series, where the powerful electron-withdrawing cyano group of compound 1 has been replaced by alkyl and phenyl groups, the order of antihypertensive potency is ethyl, isopropyl, tert-butyl greater than propyl, cyclopentyl greater than methyl greater than phenyl.

Synthesis and antihypertensive activity of 4-(substituted-carbonylamino)-2H-1-benzopyrans.

The synthesis and antihypertensive activity of a series of novel 4-(substituted-carbonylamino)-2H-1-benzopyran-3-ols, administered orally to conscious spontaneously hypertensive rats, are described. Optimum activity was observed for compounds with alkyl, amino, or aryl groups flanking the carbonyl group. Of the alkyl and amino series the most potent compounds contained the methyl and methylamino groups, respectively.

Synthesis and evaluation of a series of aryl[e]fused pyrazolo[4,3-c]pyridines with potential anxiolytic activity.

A series of pyrazolo[4,3-c]pyridines has been synthesized and evaluated as potential anxiolytic agents. Selected compounds from this series show a pharmacological profile of action different from that of diazepam. A number of the compounds possess higher affinity for central benzodiazepine receptors than diazepam, yet show less anticonvulsant activity and are less sedative.

MODFIT: a pharmacokinetics computer program.

This paper presents a computer program, MODFIT, written in FORTRAN, primarily for use on the Digital Equipment Company VAX series computers for the mathematical analysis of concentration-time data. Drug data generated from biological fluids and tissues may be fitted by a variety of different models. For many models, parameter starting estimates are program generated prior to automatic nonlinear regression analysis using a modified Davidon-Fletcher-Powell algorithm.

The effects of granisetron, ICS 205-930 and ondansetron on the visceral pain reflex induced by duodenal distension.

1. Distension of the duodenum in anaesthetized rats, by rapid application of intraluminal pressures (10-75 cmH2O), evoked falls in diastolic blood pressure and intragastric pressure. 2.

The role of specific 5-HT3 receptor antagonism in the control of cytostatic drug-induced emesis.

Work on the pharmacological effects of high-dose metoclopramide led Beecham scientists to identify the role of 5-HT3 receptors in the emetic response to cytostatic drugs and X-irradiation in animals. Further studies have confirmed and extended knowledge of the novel 5-HT3 antagonist granisetron. Dose-dependent inhibition of the 5-HT-induced Bezold-Jarisch reflex in anaesthetized rats was shown by doses of 0.

The clinical pharmacology of granisetron (BRL 43694), a novel specific 5-HT3 antagonist.

Granisetron is a novel specific 5-HT3 receptor antagonist whose effects have been evaluated in an extensive programme of volunteer studies. Single intravenous doses of 2.5-300 micrograms/kg of granisetron over 30 min, and of 40-160 micrograms/kg, administered over 3 min, were very well tolerated.

Tyramine antagonizes proctolin-induced contraction of the isolated foregut of the locust Schistocerca gregaria by an interaction with octopamine2 receptors.

1. Octopamine (OA) (10(-7)-10(-5) M) relaxed isolated foreguts. Tyramine mimicked the effects of OA but was 64x less potent.

Haemodynamic differences between cromakalim and pinacidil: comparison with nifedipine.

The effects of cromakalim (0.015, 0.03 and 0.

Inhibition by glibenclamide of the vasorelaxant action of cromakalim in the rat.

1. In rat isolated thoracic aortic rings pre-contracted with noradrenaline (10(-6) M), cromakalim (3 x 10(-7)-3 x 10(-5) M) produced concentration-related relaxation. This effect was progressively inhibited by increasing concentrations of the anti-diabetic sulphonylurea drug, glibenclamide (10(-6)-10(-5) M).