Search results for " Drug Screening"

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…

Molecular docking-based virtual drug screening revealing an oxofluorenyl benzamide and a bromonaphthalene sulfonamido hydroxybenzoic acid as HDAC6 in…

2020

HDAC6 is a crucial epigenetic modifier that plays a vital role in tumor progression and carcinogenesis due to its multiple biological functions. It is a unique member of class-II HDAC enzymes. It possesses two catalytic domains, which function independently of the overall enzyme activity. Up to date, there are only a few selective HDAC6 inhibitors with anti-cancer activity. In this study, 175,204 ligands obtained from the ZINC15 and OTAVAchemical databases were used for virtual drug screening against HDAC6. Molecular docking studies were performed for 100 selected compounds. Furthermore, the top 10 compounds obtained from docking were tested for their efficacy to inhibit the function of HDA…

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

2018

Graphical abstract

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…

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

2012

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…

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…

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…

1,2,4-Oxadiazole Topsentin Analogs with Antiproliferative Activity against Pancreatic Cancer Cells, Targeting GSK3β Kinase.

2021

A new series of topsentin analogs, in which the central imidazole ring of the natural lead was replaced by a 1,2,4- oxadiazole moiety, was efficiently synthesized. All derivatives were pre-screened for antiproliferative activity against the National Cancer Institute (NCI-60) cell lines panel. The five most potent compounds were further investigated in various pancreatic ductal adenocarcinoma (PDAC) cell lines, including SUIT-2, Capan-1, and Panc-1 cells, eliciting EC50 values in the micromolar and sub-micromolar range, associated with significant reduction of cell migration. These remarkable results might be explained by the effects of these new topsentin analogues on epithelial-to-mesenchy…

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…