Letters in Drug Design & Discovery - Volume 4, Issue 3, 2007

(-)-Epigallocatechin gallate (EGCG) has a sedative effect acting through γ-aminobutyric acid (GABA)A receptors in the brain, but it is unclear what structural components of the molecule are necessary for its action. To investigate the necessity of the galloyl group on the sedation induced by EGCG, the effect of EGCG was compared with (-)-epigallocatechin (EGC) in which the galloyl group is removed from EGCG. Intracerebrov Read More

The effect of pharmacones clathration with glycosides results in significant decrease of drug agent dosage. We investigated the clathrates of hypotensive agent Nifedipine with glycyrrhizic acid, which was prepared in molecular proportion 1:4 respectively. Present study was carried out on the calcium channels on neurons of Lymnaea stagnalis mollusc.

A rapid and efficient synthesis of estrogenic dimers, with 45% overall yield, is described. The new molecules possess two estrone units linked at position 16, with either an alkyl chain or a polyethylene glycol chain. The biological activity of these compounds was evaluated in vitro on estrogen dependent and independent human breast tumor cell lines: MCF-7 and MDA-MB-231.

In this study, we describe, for the first time, the synthesis and photophysical and microbiological investigation of ruthenium trischelate diimine complexes designed so as to possess properties specifically suited for use in Photodynamic antimicrobial chemotherapy (PACT). Of the three compounds investigated, one ([Ru(dmob)3]Cl2) has demonstrated considerable promise as a photosensitiser for use in PACT. As a result, Read More

We report the search for non-steroidal inhibitors of 17β-hydroxysteroid dehydrogenase, in particular, for types 1 and 3. The results show that the synthesised compounds based on the biphenyl backbone were good inhibitors of 17β-HSD1, but were weak inhibitors of 17β-HSD3. The compounds were evaluated against 3β-HSD but showed weak inhibition.

High throughput screening identified a pyrrolidinone containing acidic functionality as a CCR2 antagonist of modest affinity. We describe initial SAR around this hit, including solution phase parallel synthesis for analog preparation, and we describe identification and characterization of an analog subsequently selected as a viable lead molecule for further optimization.

The CYP3A4 inhibition SVM classification model achieved high prediction accuracy, which can be used as high throughput computational filter for identifying CYP3A4 inhibition liability. It's demonstrated that the distance to the separating surface in the feature space can be used as valuable confidence index for the prediction of each compound.

Lantadene D was semi-synthetically prepared by functionalizing 22β-hydroxyoleanonic acid and screened for cytotoxicity against four human cancer cell lines (HL-60, HeLa, Colon 502713 and Lung A-549). It was further evaluated for its inhibitory profile against two-stage carcinogenesis in Swiss albino mice.

Dependence can be induced and measured in vitro by using guinea-pig ileum. After a brief exposure to opioids, tissues from untreated animals, show a strong naloxone-induced contracture indicating that the cellular mechanisms of dependence may occur very rapidly following occupation of receptors and that these mechanisms operate within the myenteric plexus. Several observations indicate that acethilcoline (Ach) is invol Read More

Two new regioisomers acyclonucleosides bearing 1,2,4-triazole rings as the base moiety were synthesised with aliphatic side chain [(2-acetoxyethoxy)methyl]-bromide under solid-liquid phase transfer catalysis (S.L.P.T.C.) and under silylation method. Biological evaluation of all product revealed they were inactive against various RNA and DNA viruses in cell cultures. Structure activity relationship studies (SAR) in Read More

High throughput screening (HTS) has become a pivotal part of drug discovery for identifying potential lead molecules for specific disease targets. The success of screening is measured by several factors including the throughput and cost of the assays, but ultimately by the number of HTS hits that progress forward through the drug discovery pipeline. Miniaturization of assays by conversion from 96- to 384- to 1536- wells to wel Read More

Since its first description nearly a decade ago, mammalian target of rapamycin (mTOR) has emerged as a critical regulator of cell size and growth in normal and neoplastic conditions. Many cancers rely on mTOR pathway members for their survival, and these proteins thus form attractive targets with wide potential therapeutic indices. Understanding the role of mTOR in lymphomagenesis is complicated by the intricacy of u Read More

In this paper we report the synthesis of a new series of benzenesulfonamides and the evaluation of their binding properties on ETAh and ETBh receptor subtypes. Some new derivatives behave as selective ETAh receptor ligands and among them, 2-{[(4-chloro-3-methyl-5-isoxazolyl)amino]sulfonyl}-N-(2,4,6- trimethylphenyl)benzamide (23) was the most interesting.