scholarly journals Synthesis and high in vitro cytotoxicity of some (S,S)-ethylenediamine-N,N’-di-2-propanoate dihydrochloride esters

2014 ◽  
Vol 79 (6) ◽  
pp. 649-658 ◽  
Author(s):  
Nebojsa Pantelic ◽  
Bojana Zmejkovski ◽  
Tatjana Stanojkovic ◽  
Verica Jeftic ◽  
Gordana Radic ◽  
...  
Keyword(s):  
K562 Cells ◽  
13C Nmr Spectroscopy ◽  
In Vitro Cytotoxicity ◽  
Myelogenous Leukemia ◽  
Antitumor Action ◽  
Human Embryonic Lung ◽  
1H And 13C Nmr ◽  
Cancerous Cell ◽  
Human Embryonic Lung Fibroblast

Novel (S,S)-R2eddip ester, O,O?-diisoamyl-(S,S)-ethylenediamine-N,N?-di-2-propanoate dihydrochloride, 1, was synthesized and characterized by IR, 1H and 13C NMR spectroscopy, mass spectroscopy and elemental analysis.In vitro antitumor action of 1, and two more R2eddip esters, O,O?-dialkyl-(S,S)-ethylenediamine-N,N?-di-2-propanoate dihydrochlorides, obtained before, (alkyl = n-Bu, n-Pe; 2 and 3, respectively), was determined against cervix adenocarcinoma (HeLa), human melanoma (Fem-x), human chronic myelogenous leukemia (K562) cells, and a non-cancerous cell line human embryonic lung fibroblast (MRC-5), using MTT assay. Esters 1-3 showed higher cytotoxicity and better selectivity in comparison to cisplatin, used as reference compound. The highest activityis expressed by1,with IC50(Fem-x)value1.51 ? 0.09 ?M.

scholarly journals NEW PHARMACOLOGICALLY ACTIVE COMPOUNDS BASED ON 5-HYDROXY-7-METHOXY-2-PHENYLCHROMAN-4-ONE

2021 ◽  
Vol 3 ◽  
pp. 119-127
Author(s):  
G.M. Baisarov ◽  
◽  
S.M. Adekenov ◽  
Keyword(s):  
Nmr Spectroscopy ◽  
13C Nmr ◽  
Potassium Carbonate ◽  
13C Nmr Spectroscopy ◽  
1H And 13C Nmr ◽  
Pharmacologically Active ◽  
Pharmacologically Active Compounds ◽  
First Time

The reaction of 5-hydroxy-7-methoxy-2-phenylchroman-4-one with dibromoalkanes in acetone in the presence of potassium carbonate proceeds according to the Michael’s retro-reaction O-alkylation and leads to the formation of the corresponding 2-(bromo-alkoxy) chalcones. The structure of the synthesized compounds was confirmed by IR-, 1H- and 13C-NMR spectroscopy. The cytotoxic, hepatoprotective and anti-inflammatory effects of chalcone derivatives (2-3) were studied for the first time in vitro and in vivo.

scholarly journals Gold(I) Complexes with P-Donor Ligands and Their Biological Evaluation

Processes ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 2100
Author(s):  
Monika Richert ◽  
Renata Mikstacka ◽  
Mariusz Walczyk ◽  
Marcin Janusz Cieślak ◽  
Julia Kaźmierczak-Barańska ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Umbilical Vein ◽  
Biological Properties ◽  
Biological Evaluation ◽  
In Vitro Cytotoxicity ◽  
Myelogenous Leukemia ◽  
31P Nmr Spectroscopy ◽  
Cervix Carcinoma ◽  
Ovarian Carcinoma Cell Line

Gold(I) complexes with phosphine ligands—[Au(TrippyPhos)Cl] (1) (TrippyPhos = 1-[2-[bis(tert-butyl)phosphino]phenyl]-3,5-diphenyl-1H-pyrazole), [Au(BippyPhos)Cl]0.5CH2Cl2 (2) (BippyPhos = 5-(di-tert-butylphosphino)-1′, 3′, 5′-triphenyl-1′H-[1,4′]bipyrazole), and [Au(meCgPPh)Cl] (3) (meCgPPh = 1,3,5,7-tetramethyl-6-phenyl-2,4,8-trioxa-6-phosphaadamantane—were investigated as types of bioactive gold metallodrugs. Complexes (1)–(3) were characterized using IR, 1H, 13C, 31P NMR spectroscopy, elemental analysis and mass spectrometry (FAB-MS). Complexes of (1) and (2) exhibited substantial in vitro cytotoxicity (IC50 = 0.5–7.0 μM) against both the cisplatin-sensitive and -resistant variants of the A2780 human ovarian carcinoma cell line, as well as against the A549 human lung carcinoma, K562 chronic myelogenous leukemia, and HeLa (human cervix carcinoma) cells. However, among the compounds studied, complex (2) showed the most promising biological properties: the highest stability in biologically relevant media, selectivity towards cancer cells over the non-cancer cells (HUVEC, human umbilical vein endothelial cells), and the highest inhibitory effect on cytosolic NADPH-dependent reductases in A2780 and A2780cis cells among the gold complexes under analysis.

Antimicrobial Properties of Mono- and Di-fac-rhenium Tricarbonyl 2-Pyridyl-1,2,3-triazole Complexes

2016 ◽  
Vol 69 (5) ◽  
pp. 489 ◽  
Author(s):  
Sreedhar V. Kumar ◽  
Warrick K. C. Lo ◽  
Heather J. L. Brooks ◽  
Lyall R. Hanton ◽  
James D. Crowley
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Properties ◽  
13C Nmr Spectroscopy ◽  
1H And 13C Nmr ◽  
X Ray Crystallography ◽  
The Family ◽  
Elemental Analyses ◽  
Solid State Structures ◽  
Rhenium Tricarbonyl

A family of mono- and di-fac-rhenium tricarbonyl 2-pyridyl-1,2,3-triazole complexes with different aliphatic and aromatic substituents was synthesized in good-to-excellent yields (46–99 %). The complexes were characterized by 1H and 13C NMR spectroscopy, infrared spectroscopy, electronic (UV-visible) spectroscopy, high-resolution electrospray mass spectrometry, and elemental analyses. In four examples, the solid-state structures of the rhenium(i) complexes were confirmed by X-ray crystallography. The family of the mono- and di-rhenium(i) complexes and the corresponding 2-pyridyl-1,2,3-triazole was tested for antimicrobial activity in vitro against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) microorganisms. Agar-based disk diffusion assays indicated that most of the rhenium(i) complexes were active against Staphylococcus aureus and that the cationic rhenium(i) complexes were more active than the related neutral systems. However, in all cases, the minimum inhibitory concentrations for all the complexes were modest (i.e. 16–1024 µg mL–1).

scholarly journals Design, Synthesis and Biological Evaluation of Pentacyclic Triterpene Derivatives: Optimization of Anti-ABL Kinase Activity

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3535 ◽  
Author(s):  
Halil I. Ciftci ◽  
Mohamed O. Radwan ◽  
Safiye E. Ozturk ◽  
N. Gokce Ulusoy ◽  
Ece Sozer ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
K562 Cells ◽  
Biological Evaluation ◽  
Benzyl Ester ◽  
Myelogenous Leukemia ◽  
Pentacyclic Triterpene ◽  
Abl Kinase ◽  
Molecular Targeted Drug ◽  
Benzyl Esters

Imatinib, an Abelson (ABL) tyrosine kinase inhibitor, is a lead molecular-targeted drug against chronic myelogenous leukemia (CML). To overcome its resistance and adverse effects, new inhibitors of ABL kinase are needed. Our previous study showed that the benzyl ester of gypsogenin (1c), a pentacyclic triterpene, has anti-ABL kinase and a subsequent anti-CML activity. To optimize its activities, benzyl esters of carefully selected triterpenes (PT1–PT6), from different classes comprising oleanane, ursane and lupane, and new substituted benzyl esters of gypsogenin (GP1–GP5) were synthesized. All of the synthesized compounds were purified and charachterized by different spectroscopic methods. Cytotoxicity of the parent triterpenes and the synthesized compounds against CML cell line K562 was examined; revealing three promising compounds PT5, GP2 and GP5 (IC50 5.46, 4.78 and 3.19 μM, respectively). These compounds were shown to inhibit extracellular signal-regulated kinase (ERK) downstream signaling, and induce apoptosis in K562 cells. Among them, PT5 was identified to have in vitro activity (IC50 = 1.44 μM) against ABL1 kinase, about sixfold of 1c, which was justified by molecular docking. The in vitro activities of GP2 and GP5 are less than PT5, hence they were supposed to possess other more mechanisms of cytotoxicity. In general, our design and derivatizations resulted in enhancing the activity against ABL1 kinase and CML cells.

scholarly journals Synthesis, Crystal Structure and Bioactivity of Phenazine-1-carboxylic Acylhydrazone Derivatives

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5320
Author(s):  
Shouting Wu ◽  
Xi Liang ◽  
Fang Luo ◽  
Hua Liu ◽  
Lingyi Shen ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Condensation Reaction ◽  
Acid Hydrazide ◽  
13C Nmr Spectroscopy ◽  
X Ray Diffraction ◽  
1H And 13C Nmr ◽  
X Ray ◽  
Thiazolyl Blue Tetrazolium Bromide ◽  
Thiazolyl Blue Tetrazolium

A phenazine-1-carboxylic acid intermediate was synthesized from the reaction of aniline and 2-bromo-3-nitro-benzoic acid. It was then esterified and reacted with hydrazine hydrate to afford phenazine-1-carboxylic hydrazine. Finally, 10 new hydrazone compounds 3a–3j were obtained by the condensation reaction of phenazine-1-carboxylic acid hydrazide and the respective aldehyde-containing compound. The structures were characterized by 1H and 13C NMR spectroscopy, MS and single crystal X-ray diffraction. The antitumor activity of the target compounds in vitro (HeLa and A549) was determined by thiazolyl blue tetrazolium bromide. The results showed that compound (E)-N′-(2-hydroxy-4-(2-(piperidine-1-yl) ethoxy) benzyl) phenazine-1-carbonyl hydrazide 3d exhibited good cytotoxic activity.

Overexpression of P-glycoprotein in K562 cells does not confer resistance to the growth inhibitory effects of imatinib (STI571) in vitro

Blood ◽  
2003 ◽  
Vol 102 (13) ◽  
pp. 4499-4503 ◽  
Author(s):  
Petranel T. Ferrao ◽  
Michelle J. Frost ◽  
Shoo-Peng Siah ◽  
Leonie K. Ashman
Keyword(s):  
Tyrosine Kinases ◽  
Lymphoblastic Leukemia ◽  
Leukemic Cell ◽  
K562 Cells ◽  
Myelogenous Leukemia ◽  
Potential Contribution ◽  
Multidrug Efflux ◽  
Imatinib Resistance ◽  
P Glycoprotein

AbstractElevated expression of multidrug efflux pumps such as P-glycoprotein (Pgp) have been associated with resistance to cytotoxic drugs used in the treatment of leukemias and other cancers. Imatinib mesylate (STI-571 or Gleevec) is a potent inhibitor of the BCR/ABL and c-KIT tyrosine kinases. It has displayed considerable efficacy in treatment of patients with Philadelphia-positive acute lymphoblastic leukemia and chronic myelogenous leukemia and those with gastrointestinal stromal tumors (GISTs). However, recently imatinib-resistant relapse has emerged as a significant problem. Although a major cause of resistance appears to be point mutation in the kinase domain of the target enzyme, the potential contribution of elevated multidrug efflux activity has not been systematically evaluated. The imatinib-sensitive human leukemic cell line K562, which is dependent on the activity of BCR/ABL for survival and growth, provides a convenient system for evaluating modulation of drug activity. By expressing Pgp at high levels in these cells, we have demonstrated that this pump provides minimal protection against cell growth inhibition and apoptosis induced by imatinib. In contrast, overexpression of Bcl-xL, which blocks apoptosis, resulted in partial protection against the drug. We conclude that Pgp up-regulation is not likely to be a significant contributor to imatinib resistance. (Blood. 2003;102:4499-4503)

Arsenic Sulfide Binds c-CBL to Promote BCR-ABL Ubiquitination and Degradation In Chronic Myelogenous Leukemia.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1200-1200
Author(s):  
Jian-Hua Mao ◽  
Xiao-Yan Sun ◽  
Jian-Xiang Liu ◽  
Qun-Ye Zhang ◽  
Ping Liu ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Conflicts Of Interest ◽  
Ring Finger ◽  
E3 Ligase ◽  
K562 Cells ◽  
Myelogenous Leukemia ◽  
Arsenic Sulfide ◽  
Cbl Protein

Abstract Abstract 1200 Using immunoprecipitation (IP)-2D-nano-HPLC-MALDI-MS-MS, we identified c-CBL in association with BCR-ABL in a multi-protein complex in K562 cells. In vitro ubiquitination and mutagenesis analyses show that c-CBL serves as a specific E3 ligase for ubiquitination of BCR-ABL at K1517. Arsenic sulfide (As4S4) treatment results in increased c-CBL protein level, which promotes ubiquitination and subsequent degradation of BCR-ABL and apoptosis of K562 cells. Elevated c-CBL is necessary and sufficient to recapitulate the effect of As4S4. Interestingly, arsenic directly binds the RING finger domain of c-CBL, inhibiting its self-ubiquitination and degradation, thus leading to accumulation of c-CBL. However, this interaction between As4S4 and c-CBL does not interfere with its E3 ligase activity towards BCR-ABL. Increased c-CBL protein and BCR-ABL degradation are also observed in vivo after As4S4 administration in BCR-ABL leukemia mice. These findings provide insights into the molecular mechanisms of arsenic and its potential therapeutic applications in CML. Disclosures: No relevant conflicts of interest to declare.

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