Search results for "Antitumor"
showing 10 items of 520 documents
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…
Intrinsic fluorescence of the clinically approved multikinase inhibitor nintedanib reveals lysosomal sequestration as resistance mechanism in FGFR-dr…
2017
Background Studying the intracellular distribution of pharmacological agents, including anticancer compounds, is of central importance in biomedical research. It constitutes a prerequisite for a better understanding of the molecular mechanisms underlying drug action and resistance development. Hyperactivated fibroblast growth factor receptors (FGFRs) constitute a promising therapy target in several types of malignancies including lung cancer. The clinically approved small-molecule FGFR inhibitor nintedanib exerts strong cytotoxicity in FGFR-driven lung cancer cells. However, subcellular pharmacokinetics of this compound and its impact on therapeutic efficacy remain obscure. Methods 3-dimens…
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…
Lead optimization through VLAK protocol: New annelated pyrrolo-pyrimidine derivatives as antitumor agents
2012
Abstract The chemometric protocol VLAK was applied to predict improvement of the biological activity of pyrrolo-pyrimidine derivatives as anticancer agents, by using the NCI ACAM Database as depository of antitumor drugs with a known mechanism of action. Among the selected compounds two of these showed a good increase in the antitumor activity. These new pyrrolo-pyrimidine compounds were demonstrated effective against the full panels of NCI DTP tumour human cell lines. The derivative 8-[3-(piperidino)propyl]-4,10-dimethyl-9-phenyl-6-(methylsulfanyl)-3,4-dihydropyrimido[1,2-c]pyrrolo[3,2-e]pyrimidin-2(8H)-one reveled efficacious against the leukemia subpanel, in particular the RPMI cell line…
Synthesis and structures of some diorganotin bis(hydroxamate)s
1994
Analysis of literature data on the antitumor activity of organotin compounds reveals that R2SnX2 and their complexes containing SnO, SnN or SnS bonds often exhibit biological activity, especially if such bonds are formed by means of intramolecular coordination. Furthermore, a wide range of biological activities, from fungicidal, bactericidal and antiseptic to psychotropic and antitumor, is found to be characteristic for some organic hydroxamic acids (N-acylhydroxylamines). From this point of view the diorgantion bis-hydroxamates in this paper are of particular interest as potential biologically active antitumor drugs. Di-n-butyltin bis(N-methyl-N-p-bromobenzoylhydroxylamine) is being screen…
Anti-tumor activity of two binuclear gold(I) complexes with bridging dithiolate ligands
1986
Abstract Two new binuclear complexes of gold with bridging dithiolate ligands were synthesized and characterized: (o3PAu)2(μ-DTE) and (Et3PAu)2(μ-DMTA); H2DTE=dithioerylthritol and H2DMTA=2,5-dimer- capto-1-thia-3,4-diazole. These compounds and three gold compounds with antiarthritic activity (gold sodium thiomalate, gold thioglucose and Et3PAuCl) were tested for antitumor activity using the Ehrlich- Ascites tumor cell in mice. Only (o3PAu)e(μ-DTE) showed significant activity.
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…