Search results for "drug screening"

Novel 4-(3-phenylpropionamido), 4-(2-phenoxyacetamido) and 4-(cinnamamido) substituted benzamides bearing the pyrazole or indazole nucleus: synthesis…

2019

Based on some common structural features of known compounds interfering with p53 pathways and our previously synthesized benzamides, we synthesized new ethyl 5-(4-substituted benzamido)-1-phenyl-1H-pyrazole-4-carboxylates 26a-c, ethyl 5-(4-substituted benzamido)-1-(pyridin-2-yl)-1H-pyrazole-4-carboxylates 27a-c and N-(1H-indazol-6-yl)-4-substituted benzamides 31a,b bearing in the 4 position of the benzamido moiety the 2-phenylpropanamido or 2-phenoxyacetamido or cinnamamido groups. A preliminary test to evaluate the antiproliferative activity against human lung carcinoma H292 cells highlighted how compound 26c showed the best activity. This last was therefore selected for further studies wi…

Isoindolo[2,1-c]benzo[1,2,4]triazines: a new ring system with antiproliferative activity.

2006

Abstract A series of isoindolo-benzo-triazines of type 4 was obtained by diazotization of 2-(2-aminoaryl)-1-cyanoisoindoles 3a – j . All the synthesized derivatives were screened by the National Cancer Institute (NCI, Bethesda, USA), for in vitro antitumor activity against a 3-human cancer cell line panel consisting of MCF7 (breast), NCI-H460 (lung), and SF-268 (CNS). Derivatives 4a , f , i , j were selected to be evaluated in the full panel of about 50 human tumor cell lines derived from nine human cancer cell types and showed antiproliferative activity generally in the micromolar range. The most sensitive cell lines were: MOLT-4 and SR of the leukemia subpanel, A549/ATCC and EKVX of the n…

Porphyrin and phthalocyanine photosensitizers designed for targeted photodynamic therapy of colorectal cancer

2020

Colorectal cancer is of particular concern due to its high mortality rate count. Recent investigations on targeted phototherapy involving novel photosensitizers and drug-delivery systems have provided promising results and realistic prospects for a successful medical treatment. New research trends have been focused particularly on development of advanced molecular systems offering effective photoactive species which could be selectively delivered directly into the affected cells. Porphyrins and phthalocyanines have been considered extremely attractive for this purpose due to their molecular versatility, excellent photochemical properties and multifunctional nature. In this review it has bee…

Synthesis and Antitumor Activity of 3-(2-Phenyl-1,3-thiazol-4-yl)-1H-indoles and 3-(2-Phenyl-1,3-thiazol-4-yl)-1H-7-azaindoles

2011

Given the potent antimicrobial, antiviral, and antitumor activities of many natural products, there is an increasing interest in the synthesis of new molecules based on natural compound scaffolds. Based on a 2,4-bis(3'-indolyl)imidazole skeleton, two new series of phenylthiazolylindoles and phenylthiazolyl-7-azaindoles were obtained by Hantzsch reaction between substituted phenylthioamides and the α-bromoacetyl derivatives. Some azaindole derivatives, tested at the National Cancer Institute against a panel of ∼60 tumor cell lines derived from nine human cancer cell types, showed inhibitory effects against all cell lines investigated at micromolar to nanomolar concentrations. Two of them exh…

A Facile Synthesis of Deaza-Analogues of the Bisindole Marine Alkaloid Topsentin

2013

A series of substituted ethyl 1-[(tert-butoxycarbonyl)amino]-2-methyl-5- (1-methyl-1H-indol-3-yl)-4-[(1-methyl-1H-indol-3-yl)carbonyl]-1H-pyrrole-3-carboxylates were prepared in excellent yields (82-98%) by one-pot reactions between β-dicarbonyl compounds 12a-e and 1,2-diaza-1,3-diene (DD) 13. Derivatives 10a,c-e, deazaanalogues of the bis-indole alkaloid topsentin, screened by the National Cancer Institute (Bethesda, MD, USA) in the in vitro one dose primary anticancer assay against a panel of about 60 human tumor cell lines, showed no significant activity, with the exception of compound 9e, which showed moderate activity against the HOP-92 cell line of the non small cell lung cancer sub-p…

A New Oxadiazole-Based Topsentin Derivative Modulates Cyclin-Dependent Kinase 1 Expression and Exerts Cytotoxic Effects on Pancreatic Cancer Cells

2021

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal form of cancer characterized by drug resistance, urging new therapeutic strategies. In recent years, protein kinases have emerged as promising pharmacological targets for the treatment of several solid and hematological tumors. Interestingly, cyclin-dependent kinase 1 (CDK1) is overexpressed in PDAC tissues and has been correlated to the aggressive nature of these tumors because of its key role in cell cycle progression and resistance to the induction of apoptosis. For these reasons, CDK1 is one of the main causes of chemoresistance, representing a promising pharmacological target. In this study, we report the synthesis of new 1,2,4…

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…

Fluorescent organometallic rhodium(I) and ruthenium(II) metallodrugs with 4-ethylthio-1,8-naphthalimide ligands: Antiproliferative effects, cellular …

2018

Fluorescent 4-ethylthio-1,8-naphthalimides containing rhodium(I) N-heterocyclic carbene (NHC) and ruthenium (II) NHC fragments were synthesised and evaluated for their antiproliferative effects, cellular uptake and DNA-binding activity. Both types of organometallics triggered ligand dependent efficient cytotoxic effects against tumor cells with the rhodium(I) NHC derivatives causing stronger effects than the ruthenium (II) NHC analogues. Antiproliferative effects could also be observed against several pathogenic Gram-positive bacterial strains, whereas the growth of Gram-negative bacteria was not substantially affected. Cellular uptake was confirmed by atomic absorption spectroscopy as well…