Search results for "Assay"

Design and development of heterologous competitive immunoassays for the determination of boscalid residues

2014

Boscalid is a modern agrochemical belonging to the so-called chemical class of succinate dehydrogenase inhibitor fungicides. With the aim of developing rapid analytical screening methods for this relevant compound, we herein report the synthesis of new boscalid mimics and the study of their suitability for the production of polyclonal antibodies. Aliphatic spacer arms equivalent in length and composition were tethered at two different aromatic rings of the target molecular structure. These haptens, besides being used for immunization, were employed in the development of heterologous competitive enzyme-linked immunosorbent assays (cELISAs) in order to improve assay detectability. Direct and …

In-silico screening of new potential Bcl-2/Bcl-xl inhibitors as apoptosis modulators

2008

One of the major problems in the fight against cancer is drug-resistance, which, at a molecular level, can be acquired through mutations able to deactivate apoptosis. In particular, proteins in the Bcl-2 family are central regulators of programmed cell death, and members that inhibit apoptosis, such as Bcl-xl and Bcl-2, are overexpressed in many tumours. The development of new inhibitors of these proteins as potential anticancer therapeutics represents a new frontier. In this work, we carried out an in-silico screening of compounds from a free database of more than 2 million structures (ZINC database), which allowed us to identify 17 sulfonamide derivatives as new potential inhibitors; thes…

Concentration dependent effects of commonly used pesticides on activation versus inhibition of the quince (Cydonia Oblonga) polyphenol oxidase

2009

Polyphenol oxidase (PPO) catalyzes the oxidation of o-diphenols to their respective quinones which undergo autopolymerization and form dark pigments. The interaction of PPO with various substrates and effectors remains the focus of intensive investigations due to the enzyme's key role in pigments biosynthesis including animal melanogenesis and fruit/fungi enzymatic browning. In this study, the effect of a range of commonly used pesticides on the enzyme activity has been evaluated using the purified quince (Cydonia oblonga Miller) PPO. The biochemical analysis showed that, in the presence of high pesticide concentrations, the enzyme was competitively inhibited, particularly with benomyl, car…

Proteomic identification of protease cleavage sites characterizes prime and non-prime specificity of cysteine cathepsins B, L, and S.

2011

Cysteine cathepsins mediate proteome homeostasis and have pivotal functions in diseases such as cancer. To better understand substrate recognition by cathepsins B, L, and S, we applied proteomic identification of protease cleavage sites (PICS) for simultaneous profiling of prime and non-prime specificity. PICS profiling of cathepsin B endopeptidase specificity highlights strong selectivity for glycine in P3' due to an occluding loop blocking access to the primed subsites. In P1', cathepsin B has a partial preference for phenylalanine, which is not found for cathepsins L and S. Occurrence of P1' phenylalanine often coincides with aromatic residues in P2. For cathepsin L, PICS identifies 845 …

Identification of potential inhibitors targeting BRAF-V600E mutant melanoma cells.

2020

Indicaxanthin, a multi-target natural compound from Opuntia ficus-indica fruit: From its poly-pharmacological effects to biochemical mechanisms and m…

2019

Abstract Over the latest years phytochemical consumption has been associated to a decreased risk of both the onset and the development of a number of pathological conditions. In this context indicaxanthin, a betalain pigment from Opuntia ficus-indica fruit, has been the object of sound research. Explored, at first, for its mere antioxidant potential, Indicaxanthin is now regarded as a redox-active compound able to exert significant poly-pharmacological effects against several targets in a number of experimental conditions both in vivo and in vitro. This paper aims to provide an overview on the therapeutical effects of indicaxanthin, ranging from the anti-inflammatory to the neuro-modulatory…

Design and Synthesis of 4-Substituted Indolo[3,2-e][1,2,3]triazolo[1,5-a]pyrimidine Derivatives with Antitumor Activity

2008

New derivatives of the indolo[3,2- e][1,2,3]triazolo[1,5- a]pyrimidine system, substituted in the 4 position, were designed as novel antitumor agents because of their theoretical capability to form stable complexes with DNA fragments. The calculated free energies of binding were found in the range -12.76 --> -39.68 Kcal/mol. The docking studies revealed a common binding mode with the chromophore intercalated between GC base pairs, whereas the side chain lies along the minor groove. Compounds, selected on the basis of the docking studies and suitably synthesized, showed antiproliferative activity against each type of tumor cell line investigated, generally in the low micromolar range. The mo…

Nano-materials for use in sensing of salmonella infections: Recent advances

2016

Salmonella infectious diseases spreading every day through food have become a life-threatening problem for millions of people and growing menace to society. Health expert's estimate that the yearly cost of all the food borne diseases is approximately $5-6 billion. Traditional methodologies for salmonella analysis provide high reliability and very low limits of detection. Among them immunoassays and Nucleic acid-based assays provide results within 24h, but they are expensive, tedious and time consuming. So, there is an urgent need for development of rapid, robust and cost-effective alternative technologies for real-time monitoring of salmonella. Several biosensors have been designed and comm…

Synthesis and antiproliferative activity of new derivatives containing the polycyclic system 5,7:7,13-dimethanopyrazolo[3,4-b]pyrazolo[3’,4’:2,3]azep…

2013

The reaction under reflux between 1-phenyl-3-R-5-methylaminopyrazoles and 2,5-hexanedione lead to 5,7:7,13-dimethanopyrazolo[3,4-b]pyrazolo[3′,4′:2,3]azepino[4,5-f]azocine derivatives 3b–g. These unusual molecules show the structural complexity of many biologically active natural products and are endowed with the chemical diversity that is required in drug discovery. The compounds 3b,e were reduced by hydrogen in the presence of Palladium on activated charcoal to give the dihydro derivatives 5b,e. Compounds 3b–f and 5b,e were selected by the NCI to evaluate their in vitro antiproliferative activity against 60 human cell lines derived from nine clinically isolated cancer types (leukaemia, lu…

N-(INDAZOLYL)BENZAMIDO DERIVATIVES AS CDK1 INHIBITORS: DESIGN, SYNTHESIS, BIOLOGICAL ACTIVITY, AND MOLECULAR DOCKING STUDIES

2009

A series of N-1H-indazole-1-carboxamides has been synthesized and their effects on both CDK1/cyclin B and the K-562 (human chronic myelogenus leukemia) cell line were evaluated. Using a computational model, we have observed that all the most active compounds 9e, f, i-n exhibited the same binding mode of purvanalol A in the ATP-binding cleft. Although they were able to moderately inhibit the leukemic cell line K-562 and to show inhibitory activity against the Cdc2-Cyclin B kinase in the low micromolar range, they turned out to be non-cytotoxic against HuDe (IZSL) primary cell cultures from human derm. These preliminary results are quite encouraging in view of the low toxicity demonstrated by…