Search results for " Drug Screening"

Inkjet printing arrays and their applications for drug screening

2010

Aza-isoindolo and isoindolo-azaquinoxaline derivatives with antiproliferative activity

2015

Abstract Three new ring systems, pyrido[2′,3′:3,4]pyrrolo[1,2- a ]quinoxalines, pyrido[3′,2′:3,4]pyrrolo[1,2- a ]quinoxalines and pyrido[2′,3′:5,6]pyrazino[2,1- a ]isoindoles, were synthesized through an aza-substitution on the already active isoindolo-quinoxaline system and in particular in the position 7 or 4 of the isoindole moiety and in position 5 of the quinoxaline portion. All new compounds were screened by the National Cancer Institute (Bethesda, MD) against a panel of 60 human tumor cell lines. Biological results of the most active derivatives, with pGI 50 values between 7.09 and 7.27, confirmed the importance of the presence of methoxy substituents for biological activity. The ant…

High-throughput screening at the picoliter scale by combining Dip Pen Lithography with Inkjet printing

Drug screening is a complex, expensive and time consuming field consisting of diseasebased target identification in conjunction with high-throughput screening of chemical and natural product libraries. Conventional drug screening technology is usually time and reagent consuming (micro-, nanoliter scale) and is based on complex liquid handling robotics. In this work, we show a low-cost and miniaturized drug screening methodology based on direct bio-printing methodologies like Inkjet Printing and Dip Pen Lithography. We show the possibility to precisely deliver femtoliter scale droplets of protein targets by Dip Pen Lithography by finely tuning deposition parameters. This allows obtaining mic…

Ink-Jet Printing for drug srreening on microarrays: from covalent approaches to in-liquid-droplets assays

2012

Drug screening is the complex process of retrieving chemical compounds able to modulate the activity of biological targets which are of interest for certain diseases. Conventional miniaturized drug screening technologies are based on robotic dispensers coupled with microwell arrays. However these devices require time and reagent consuming (micro-, nanoliter scale) instrumental tools, liquid handling robotics and complex detectors. Here we show a low-cost and efficient drug screening methodology based on inkjet printing for delivering molecular systems in picoliter volumes coupled with easily-implemented detection tools for probing target-drug interaction. We firstly show up a screening plat…

Droplet-to-droplet microarray for drug screening in picoliter scale

2012

Synthesis of Triazenoazaindoles: a New Class of Triazenes with Antitumor Activity

2011

Despite improvements in the treatment and prevention of cancer, the number of new diagnoses continues to rise; this has fuelled substantial interest in the development of new and effective chemotherapeutic agents. Compounds of the triazene class, such as dacarbazine, have been used in the clinical management of many cancer types including brain, leukemia, and melanoma. A new compound class bearing a triazenoazaindole scaffold was synthesized with the aim of identifying new antiproliferative agents. Compounds 5 a-g and 6 a-c were screened against a panel of human tumor cell lines, and two of them, 5 e and 5 f, showed cytotoxicity (GI(50) range: 2.2-8.2 μM) in all cell lines. These two compou…

Pyrrolo[2',3':3,4]cyclohepta[1,2-d][1,2]oxazoles, a New Class of Antimitotic Agents Active against Multiple Malignant Cell Types

2020

A new class of pyrrolo[2',3':3,4]cyclohepta[1,2-d][1,2]oxazoles was synthesized for the treatment of hyperproliferative pathologies, including neoplasms. The new compounds were screened in the 60 human cancer cell lines of the NCI drug screen and showed potent activity with GI50 values reaching the nanomolar level, with mean graph midpoints of 0.08-0.41 μM. All compounds were further tested on six lymphoma cell lines, and eight showed potent growth inhibitory effects with IC50 values lower than 500 nM. Mechanism of action studies showed the ability of the new [1,2]oxazoles to arrest cells in the G2/M phase in a concentration dependent manner and to induce apoptosis through the mitochondrial…

Novel iodoacetamido benzoheterocyclic derivatives with potent antileukemic activity are inhibitors of STAT5 phosphorylation

2016

Signal Transducer and Activator of Transcription 5 (STAT5) protein, a component of the STAT family of signaling proteins, is considered to be an attractive therapeutic target because of its involvement in the progression of acute myeloid leukemia. In an effort to discover potent molecules able to inhibit the phosphorylation-activation of STAT5, twenty-two compounds were synthesized and evaluated on the basis of our knowledge of the activity of 2-(3’,4’,5’-trimethoxybenzoyl)-3-iodoacetamido-6-methoxy benzo[b]furan derivative 1 as a potent STAT5 inhibitor. Most of these molecules, structurally related to compound 1, were characterized by the presence of a common 3’,4’,5’-trimethoxybenzoyl moi…

A selective inhibitor of the Polo-box domain of Polo-like kinase 1 identified by virtual screening

2018

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Micro and Nano patterns for Biosensing: from enzymatic assays to single cells interaction arrays

2012

In this thesis work, solution dispensing techniques have been employed for the realization of complex biological arrays. Inkjet printing techniques were employed for the generation of drug screening platforms. This approach was initially proved with a model enzyme system like Glucose Oxidase substrate covalently linked to a functionalized silicon oxide support. On this support an enzymatic substrate (D-glucose)/inhibitor (D-glucal) couple was accurately dispensed. A simple optical detection method was used to prove the screening capability of the microarray with the possibility to assay with high reproducibility at the single spot level. Afterwards, this methodology has been extended to CYP…