Showing papers in "Letters in Drug Design & Discovery in 2005"

Szeged Index - Applications for Drug Modeling&#

Abstract: In this review we describe various applications of Szeged (Sz) index for modeling physicochemical properties as well as physiological activities of organic compounds acting as drugs or possess pharmacological activity. © 2005 Bentham Science Publishers Ltd.

Novel Benzo[1,2-c]1,2,5-Oxadiazole N-Oxide Derivatives as Antichagasic Agents: Chemical and Biological Studies

Abstract: This research was supported by FONDECYT 1000834, 7040037, 1020095, CSIC (UdelaR), CLEMENTE ESTABLE and TWAS grants. We thank a scholarship for C. Rigol from RELACQ.

A facile synthesis of C2-substituted pyrrolo[2,3-f]quinolines with cytotoxic activity

Abstract: An expeditious four-step synthesis of the 1H-pyrrolo[2,3-f]quinoline-2- carboxamides (5a-h) is described. Readily available 6-quinolinecarboxaldehyde is converted to the parent acid (6) by nucleophilic attack of the azido-ester (9) and intramolecular cyclization of (10) followed by hydrolysis of the methyl ester (11). The cytotoxicity of the target molecules (5a-h) was evaluated in four tumour cell lines in vitro. One compound (5d) showed sufficient activity (IC50 = 10.2 ?M) in the human non-small cell lung cell line NSCLC-N16-L16 to be worthy of further study.

Synthesis and Cyclooxygenase-2 (COX-2) Inhibiting Properties of 1,5 - Diarylpyrazoles Possessing N-Substitution on the Sulfonamide (-SO2NH2) Moiety †

Abstract: A number of novel 1,5-diarylpyrazoles possessing N-substitution on the sulfonamide (-SO2NH2) moiety were synthesized and tested for COX-1/COX-2 inhibition in vitro. Many of these 1,1-dioxo-2,3- dihydrobenzo(d)isothiazolyl substituted 1,5-diarylpyrazoles, where the SO2NH2 group was a part of the fused ring, showed COX inhibitory activity. Few of them were identified as selective COX-2 inhibitors. Structure Activity Relationship study within the series are discussed.

In-Vitro Searching for a New Potent Reactivator of Acetylcholinesterase Inhibited by Nerve Agent VX

Abstract: Organophosphorus compounds, especially nerve agents, inhibit enzyme acetylcholinesterase(AChE; EC 3.1.1.7) in an irreversible manner. Atropine plus an oxime reactivator are used as an effectivetreatment of organophosphate poisoning. In this work, we have evaluated reactivation potency of twentyreactivators of different chemical structures in reactivation of VX-inhibited AChE. Rat brain AChE homogenatewas used as the appropriate source of the enzyme. According to our results, trimedoxime seems to be the mostpotent reactivator of VX-inhibited AChE at the concentration 10 -3 M. Keywords: Nerve agent, reactivation, inhibition, acetylcholinesterase, trimedoxime, oxime, VX agent. INTRODUCTION organophosphate poisoning. Oxime reactivators break thebond between enzyme and organophosphate and restore thefunctional enzyme (Scheme 1 – Reactivation). However,none from the currently used AChE reactivators is able tosatisfactorily reactivate AChE inhibited by all kinds of OPs[2a].Organophosphorus compounds (OPs) have been widelyused as pesticides in many parts of the world and have beenalso misused as chemical warfare agents [1]. From thisgroup, nerve agents are the most known [2]. In the past, theywere also used in terroristic attack in Tokyo subway [3].Therefore, the threat of the intoxication with OPs isrelatively high. The most potent nerve agents are representedMany laboratories over the world are interested in thesynthesis of the so-called “broad spectrum” reactivator that