Letters in Drug Design & Discovery - Volume 8, Issue 2, 2011

Multidrug resistant (MDR) bacteria constitute an ever-increasing threat to public health. The main mechanism of MDR is the active expulsion of drugs by bacterial pumps that expel unrelated compounds. The increase of knowledge, the understanding of efflux-mediated resistance and the translation of it into the development of original antimicrobials constitute important areas to report new results. The prevalence and the Read More

Multi-drug resistance (MDR) of Gram-negative and Gram-positive bacteria is strongly associated with a modification of membrane permeability that alters the intracellular concentration of antimicrobial agents such as antibiotics, antiseptics and biocides. In order to combat this bacterial strategy, coordinated efforts from diverse and complementary scientific areas are essential - from clinical bacteriology, bacterial physiology, met Read More

A survey on MDR modulators containing heterocyclic moiety in the chemical structure for the past 20 years is provided. The discussion of the particular active compound is classified according to the heterocyclic rings involved. The most important biological results are also summarized.

Multidrug resistance (MDR) to antibiotics presents a serious therapeutic problem in the treatment of bacterial infections. The importance of this mechanism of resistance in clinical settings is reflected in the increasing number of reports of multidrug resistant isolates. In Salmonella enterica, the most common etiological agent of food borne salmonellosis worldwide, MDR is becoming a major concern. In Salmonella the main Read More

The 3-[2-(dimethylamino)ethyl]-6-nitroquinazolin-4(3H)-one (BG1188) may modify the antibiotic susceptibility of human Gram-negative bacteria which present multidrug resistant phenotype. This application requires to know the time stability of BG1188 solutions. This paper reports for the first time about the time stability of the BG1188 solutions measured by optical absorption; the solvents were ultrapure de-ionized water Read More

Pulmonary tuberculosis infections caused by multi-drug resistant Mycobacterium tuberculosis has progressed to extensively drug resistant status (XDR-TB). XDR-TB is very difficult to treat successfully and results in high mortality. Globally, XDR-TB is now a major threat, especially to India and countries that were once part of the Soviet Union. There is a potential alternative to current ineffective therapy that is solidly supported Read More

A quorum is the smallest number of people able to organize the decisions concerning functional activity. Similarly microbes use chemical signal molecules to make population size-dependent “decisions” by changing their gene regulations. The inhibition of quorum sensing (QS) by phenothiazines and structurally related molecules, e.g. amitriptyline, promethazine, acridine orange, imipramine, promazine, diethazine, Read More

Background: Multidrug resistance modifiers were indentified against ABC transporters such as ABCB1, but there are other resistance mechanisms based upon such transporters as CTR1 or ATP7A/B membrane proteins. Cisplatin resistance due to the lower expression of CTR1 or to the over-expression of ATP7A/B is also responsible for therapeutic failures in many cancer types. Materials and Methods: 35 modified steroid deri Read More

This study aimed at analyzing the relationship between the expression of P-gp, MRP, LRP, GST-π and TopoIIα and acquired resistance to cisplatin in lung adenocarcinoma cell line A549. Drug resistance to cisplatin was determined using MTT assays. The expressions of P-gp, MRP, LRP, GST-π and TopoIIα were measured by immunofluorescence, Western blot and RT-PCR. The results showed that there was a significant elevation of I Read More

Two series of gemfibrozil chiral analogues were synthesized and evaluated for their agonistic activity on PPARα receptor, belonging to the transcription factor family. A simple method to synthesize ureidic and thioureidic fibrates is described. Their ability to interact with the PPARα receptor was evaluated by a transactivation assay in comparison with gemfibrozil, with the aim of obtaining new hypolipidemic compou Read More

A web-based G-protein coupled receptor (GPCR) ab initio modeling platform has been developed to support scientists involved in internal in silico drug discovery projects. Starting from a target GPCR sequence, the ab initio modeling workflow predicts an ensemble of 3-dimensional (3D) receptor structures which can subsequently be used for structure- based drug design activities. The workflow used to develop the web-b Read More

Molecular topology and multilinear regression analysis have been applied to achieve QSAR models for the prediction of the in vitro antiprotozoal activity against T. b. rhodesiense, P. falciparum as well as the cytotoxicity of a group of compounds analogs to pentamidine. Once the models were validated, a molecular screening was carried out for the search of new compounds showing high activity on both parasites and low cytotoxicity.

Panax ginseng C. A. Meyer (PG), a well-known traditional Chinese medicine, has been widely used as a panacea in treatment of human diseases for a long time. In this study, we exerted systems biology and bioinformatics methods for the first time and analyzed the “giant components” of PG in the global component-target interaction network. Based upon this network, we further confirmed several key components and their rela Read More

The reaction of 2-(aryloxymethyl)benzoic acid hydrazide with carbon disulfide in the presence of potassium hydroxide followed by hydrazine hydrate afforded 4-amino-3{2-(aryloxymethyl)pheny}[1,2,4]triazole-5-thiol (5a-d). The cyclo-condensation of 5a-d with various aromatic carboxylic acids in the presence of phosphorous oxychloride and with phenacyl bromides afforded two series of fused heterocycles namely; 6-subs Read More