2,3-Dihydroimidazo[1,2-b]ferroceno[d]pyridazines and a 3,4-dihydro-2H-pyrimido[1,2-b]ferroceno[d]pyridazine: Synthesis, structure and in vitro antiproliferation activity on selected human cancer cell lines

Csókás, Dániel; Károlyi, Benedek Imre; Bősze, Szilvia; Szabó, Ildikò; Báti, Gábor; Drahos, László; Csámpai, Antal

doi:10.1016/j.jorganchem.2013.10.057

Cited by 20 publications

(10 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: Resultsmentioning

confidence: 99%

“…Prompted by the aforementioned highly promising precedents, in the frame of our ongoing research aimed at identification of novel leads including ferrocene hybrids [22][23][24][25][26][27][28][29] we envisaged atryptamine-and tryptophan-based synthesis, detailed structural analysis and preliminary in vitro evaluation of 6-aryl-substituted 5,6,8,9,14,14b-hexahydroindolo[2',3':3,4]pyrido [1,2-c]quinazolines (I), 5,5b,17,18-tetrahydroindolo [2',3':3,4]pyrido [1,2-c]isoindolo[2,1-a]quinazolin-11(15bH)-ones (II), and (Sp)-2-formyl-1-ferrocenecarboxylate-derived 5,5b, 11,14b,16,17- A straightforward retrosynthetic analysis of pentacycles type I set up an obvious synthetic pathway starting with a Pictet-Spengler (PS) annelation involving tryptophan-based precursors and Molecules 2020, 25, 1599 3 of 25 2-nitrobenzaldehyde followed by nitro group reduction and subsequent aldehyde-mediated cyclisation of the resulting 2-aminophenyl-substituted β-carboline framework to construct the targeted pentacyclic products (Scheme 1). Accordingly, tryptamine (1) was first converted into the nitrophenyl derivative 3 by an efficient PS protocol using an acetic acid/boric acid system at reflux temperature to promote the reaction [30] which practically went to completion within 4 h and allowed the isolation of the product as a racemic mixture in 85% yield.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Novel Polycondensed Partly Saturated β-Carbolines Including Ferrocene Derivatives: Synthesis, DFT-Supported Structural Analysis, Mechanism of Some Diastereoselective Transformations and a Preliminary Study of their In Vitro Antiproliferative Effects

et al. 2020

Self Cite

View full text Add to dashboard Cite

Use of a Pictet-Spengler reaction of tryptamine and l-tryptophan methyl ester and subsequent reduction of the nitro group followed by further cyclocondensation with aryl aldehydes and formyl–substituted carboxylic acids, including ferrocene-based components, furnished a series of diastereomeric 6-aryl-substituted 5,6,8,9,14,14b-hexahydroindolo[2′,3′:3,4]pyrido[1-c]-quinazolines and 5,5b,17,18-tetrahydroindolo[2′,3′:3,4]pyrido[1,2-c]isoindolo[2,1-a]quinazolin-11-(15bH)-ones with the elements of central-, planar and conformational chirality. The relative configuration and the conformations of the novel polycyclic indole derivatives were determined by 1H- and 13C-NMR methods supplemented by comparative DFT analysis of the possible diastereomers. The structure of one of the pentacyclic methyl esters with defined absolute configuration “S” was also confirmed by single crystal X-ray diffraction measurement. Accounting for the characteristic substituent-dependent diastereoselective formation of the products multistep mechanisms were proposed on the basis of the results of DFT modeling. Preliminary in vitro cytotoxic assays of the products revealed moderate-to-significant antiproliferative effects against PANC-1-, COLO-205-, A-2058 and EBC-1 cell lines that proved to be highly dependent on the stereostructure and on the substitution pattern of the pending aryl substituent.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Novel Polycondensed Partly Saturated β-Carbolines Including Ferrocene Derivatives: Synthesis, DFT-Supported Structural Analysis, Mechanism of Some Diastereoselective Transformations and a Preliminary Study of their In Vitro Antiproliferative Effects

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Unfortunately, the use of transition metal in chemotherapy is often accompanied with severe side effects [30]. Aiming to overcome the toxic limitations and to broaden the scope of treatable malignancies, research lead to the discovery of one of the fused ferrocene derivatives, (Sp)-ferroceno[d]pyridazine [31] (cpd 2), it's in vitro antitumour activity was investigated against HepG2 hepatoma and HT-29 colorectal adenocarcinoma cell cultures by (MTT) assay.…”

Section: Dna Chelatorsmentioning

confidence: 99%

Pyridazine Based Scaffolds as Privileged Structures in anti-Cancer Therapy

2017

View full text Add to dashboard Cite

Pyridazines, their oxo derivatives; pyridazinone as well as fused bi- or tricyclic pyridazine containing scaffolds are key structural features of many biologically active compounds with diverse pharmacological applications, including cancer therapy. Since protein kinases play prominent role in tumor biology, the inhibition of its signaling pathway is considered an effective therapeutic option for the treatment of cancer.Based on the various advantages of pyridazines in drug design including modulation of the physico-chemical properties, improving ADME and toxicity profile as well as easy and diverse synthetic methods of access, makes them an invaluable tool for designing compounds as future drugs for targeted cancer treatment.In this review, we have compiled and discussed the anticancer potential of pyridazine based scaffold, with special focus on those targeting protein kinase inhibition.

show abstract

“…The effect of stereochemistry on biological activity is of great importance in medicinal chemistry, as many of the biological targets are chiral [30,31]. The anticancer properties of chiral metal derivatives have been largely studied [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46], but the role of the stereochemistry in the biological activity of non-platinum based compounds has been less investigated [22,[47][48][49][50][51][52][53][54][55][56][57][58][59][60][61]. Effect of the absolute configuration on the anticancer efficiency of titanium compounds was firstly explored by Tshuva in 2010 [50].…”

Section: Introductionmentioning

confidence: 99%

Study of the anticancer properties of optically active titanocene oximato compounds

Cueva-Alique

Sierra

Pérez‐Redondo

et al. 2019

Journal of Organometallic Chemistry

View full text Add to dashboard Cite

New water soluble and optically active cyclopentadienyl titanium derivatives [(η 5-C 5 H 5) 2 Ti{(1R,4S)-ĸON,(R)NH}Cl] (R = Bn (Benzyl) 1a', 2-pic (2-picolylamine) 1b') have been synthesized. The novel compounds along with those previously described [(η 5-C 5 H 5) 2 Ti{(1S,4R)-ĸON,(R)NH}Cl] (R = Bn 1a, 2-pic 1b) were evaluated by polarimetry, ultraviolet and circular dichroism spectroscopy. The structure of 1b was determined by single crystal X-ray crystallography and showed a unique terminal monohapto Ti-O disposition of the oximato ligand. All enantiomers have been tested against several cancer cell lines in vitro: prostate PC-3 and DU-145, lung A-549, pancreas MiaPaca-2, colorectal HCT-116, leukemia Jurkat and cervical HeLa. In addition, 1a, 1b and 1b' were tested against non-tumorigenic prostate RWPE-1 cell line. After 24 h of incubation, 1b and 1b' were moderately active against Jurkat and A-549 cells. The anti-proliferative effect of titanium compounds on prostate PC-3, DU-145 and RWPE-1 cell lines was also assessed after 72 h of drug exposure. The cytotoxic profile of the enantiomers was similar, exception made for the PC-3 cells, with S,R-isomers exhibiting cytotoxicities 2 to 3 times higher than R,S-compounds. Under these conditions, derivative 1b showed calculated IC 50 values better than those of Tacke´s Titanocene-Y (bis-[(p-methoxybenzyl)cyclopentadienyl]titanium(IV) dichloride) on both the prostate PC-3 and DU-145 cells. 1a and 1b cytotoxic behaviour shows certain selectiveness, with activities 2-4 times lower on normal prostate RWPE-1 than on cancer PC-3 cells. Furthermore, 1b produces higher cytotoxicity on prostate PC-3, DU-145 and RWPE-1 cells than the additive dose of titanocene dichloride and pro-ligand b•HCl. Additionally, compound-DNA interactions have been investigated by equilibrium dialysis, Fluorescence Resonance Energy Transfer (FRET) melting assays and viscometric titrations, which suggest that these metal complexes and/or their hydrolysis products bind DNA either in the minor groove or externally. Highlights (85 characters) • Synthesis of novel enantiopure titanocene amino-oximato compounds is reported. • The X-ray crystal structure of one of the compounds shows a unique monohapto Ti-ON coordination. • One enantiomer shows IC 50 values lower than Titanocene-Y on both PC-3 and DU-145 cells. • One enantiomer is more active than additive doses of Ti(η 5-C 5 H 5)Cl 2 and oxime pro-ligand.

show abstract

2,3-Dihydroimidazo[1,2-b]ferroceno[d]pyridazines and a 3,4-dihydro-2H-pyrimido[1,2-b]ferroceno[d]pyridazine: Synthesis, structure and in vitro antiproliferation activity on selected human cancer cell lines

Cited by 20 publications

References 69 publications

Novel Polycondensed Partly Saturated β-Carbolines Including Ferrocene Derivatives: Synthesis, DFT-Supported Structural Analysis, Mechanism of Some Diastereoselective Transformations and a Preliminary Study of their In Vitro Antiproliferative Effects

Novel Polycondensed Partly Saturated β-Carbolines Including Ferrocene Derivatives: Synthesis, DFT-Supported Structural Analysis, Mechanism of Some Diastereoselective Transformations and a Preliminary Study of their In Vitro Antiproliferative Effects

Pyridazine Based Scaffolds as Privileged Structures in anti-Cancer Therapy

Study of the anticancer properties of optically active titanocene oximato compounds

Contact Info

Product

Resources

About