Search results for " ANTIPROLIFERATIVE ACTIVITY"
showing 10 items of 58 documents
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 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…
Novel antiproliferative chimeric compounds with marked histone deacetylase inhibitory activity.
2014
Given our interest in finding potential antitumor agents and in view of the multifactorial mechanistic nature of cancer, in the present work, taking advantage of the multifunctional ligands approach, new chimeric molecules were designed and synthesized by combining in single chemical entities structural features of SAHA, targeting histone deacetylases (HDACs), with substituted stilbene or terphenyl derivatives previously obtained by us and endowed with antiproliferative and pro-apoptotic activity. The new chimeric derivatives were characterized with respect to their cytotoxic activity and their effects on cell cycle progression on different tumor cell lines, as well as their HDACs inhibitio…
Synthesis and antiproliferative activity of indazole derivatives
2011
Indazole nucleus represents a very attractive scaffol to obtain new molecole endowed with antineoplastic activity. On the basis of these literature data we have designed some indazole derivatives such as N-indazolylbenzamides and N-indazolyl-N’-phenylureas as potential CDK1 inhibitors. In fact the above compounds contain the structural feature, common to the majority of CDK inhibitors, requested to make hydrogen bonds with the molecular forks present in the hinge region of CDKs. The N-indazolylbenzamides 1 were obtained by reacting aminoindazoles and substituted benzoylchlorides. Among the synthesized compounds some derivatives 1 resulted to be CDK1 inhibitors showing IC50 values in the ran…
Cytotoxic properties of Marrubium globosum ssp. libanoticum and its bioactive components
2013
Marrubium globosum Montbr. et Auch. ex Benth. ssp. libanoticum Boiss. (Lamiaceae) is a medicinal plant used in Lebanon for the treatment of inflammatory diseases, asthma, coughs and other pulmonary and urinary problems. The goal of our study was to assess the biological activity of M. globosum by testing different extracts of the aerial parts for their antiproliferative activity against human melanoma cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The chloroform fraction showed the greatest activity. The compounds isolated from the extracts were also tested: the mixture of (13 S)-9α,13α-epoxylabda-6β(19),16(15)-diol dilactone and (13 R)-9α,13α-epo…
FUSED NITROGEN HETEROCYCLES AS PROMISING SMALL MOLECULES FOR THE TREATMENT OF CANCER
2020
Synthesis and antioproliferative activity of new derivatives containing the policyclic sistem 5,7:7,13-dimethanopyrazolo[3,4-b]pyrazolo[3'.4':2,3]aze…
2012
By reacting methylaminopyrazoles with hexane-2,5-dione in 1,4-dioxane in the presence of p-toluensulfonic acid, new derivatives containing the policyclic sistem 5,7:7,13-dimethanopyrazolo[3,4-b]pyrazolo[3'.4':2,3]azepino[4,5-f]azocine were obtained. The new synthesized compounds were tested preliminarly at 10 microM against five human cancer cell lines showing a range of inhibition of 20-62% against the most susceptible cell lines K562 and HCT116.
Synthesis of a new class of pyrrolo[3,4-h]quinazolines with antimitotic activity
2014
Abstract A new series of pyrrolo[3,4- h ]quinazolines was conveniently prepared with a broad substitution pattern. A large number of derivatives was obtained and the cellular cytotoxicity was evaluated in vitro against 5 different human tumor cell lines with GI 50 values reaching the low micromolar level (1.3–19.8 μM). These compounds were able to induce cell death mainly by apoptosis through a mitochondrial dependent pathway. Selected compounds showed antimitotic activity and a reduction of tubulin polymerization in a concentration-dependent manner. Moreover, they showed anti-angiogenic properties since reduced in vitro endothelial cell migration and disrupted HUVEC capillary-like tube net…
Pyrazolo[3,4-h]quinolines promising photosensitizing agents in the treatment of cancer.
2015
A new series of pyrazolo[3,4-h]quinolines, heteroanalogues of angelicin was conveniently prepared with a broad substitution pattern. A large number of derivatives was obtained and the cellular photocytotoxicity was evaluated in vitro against 5 different human tumor cell lines with GI50 values reaching the nanomolar level (14.52e0.04 mM). Selected compounds were able to photoinduce a massive cell death with the involvement of mitochondria. Their photodamage cellular targets were proteins and lipids and they did not cause any kind of DNA photodamage. This latter event is of considerable importance in the modulation of long term side effects, generally associated with the use of classical furo…
An efficient synthesis of pyrrolo[3',2':4,5]thiopyrano[3,2-b]pyridin-2-one: a new ring system of pharmaceutical interest
2012
Abstract A series of pyrrolo[3′,2′:4,5]thiopyrano[3,2- b ]pyridin-2-ones 4 was prepared in good yields by reacting enaminoketones with cyanomethylene active compounds such as phenylsulfonylacetonitrile, benzoylacetonitrile, and malononitrile. Derivatives of the title ring system were tested by the National Cancer Institute of Bethesda against a panel of about 60 human tumor cell lines, and one of them showed inhibitory activity against all cancer cell lines reaching on 48% of them GI 50 values at submicromolar level and on the majority of the remaining ones in the low micromolar concentration.