Metal complexes with new types of chiral ligands based on natural terpenes

Ларионов, С. В.

doi:10.1134/s1070328412010058

Cited by 28 publications

(8 citation statements)

References 46 publications

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“…2) [48,63,64], derived from R-limonene. This naturally occurring terpene is an inexpensive starting reagent, commercially available in optically pure form and easily tailored by stereoselective functionalization [63–65]. …”

Section: Introductionmentioning

confidence: 99%

Novel enantiopure cyclopentadienyl Ti(IV) oximato compounds as potential anticancer agents

Cueva-Alique

Muñoz-Moreno

Benabdelouahab

et al. 2016

Journal of Inorganic Biochemistry

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The synthesis and characterization of new enantiopure cyclopentadienyl titanium oximato compounds (S,R)-[(η5-C5H5)Ti{κ2NO,(R)NH·HCl}Cl2] (R = Ph (phenyl) 1a·HCl, Bn (benzyl) 1b·HCl, 2-pic (2-picolyl) 1c·HCl), (S,R)-[(η5-C5H5)TiCl2{κ2NO,(Ph)NH}] (1a) and (S,R)-[(η5-C5H5)2TiCl{κ2NO,(R)NH}] (R = Ph 2a, Bn 2b, 2-pic 2c), along with studies on their behaviour in D2O at different pD values are reported. The structure of previously described ammonium-oxime (2S,5R)-{NOH,(Bn)NH·HCl} (b·HCl) and novel titanium derivative 1a have been determined by single crystal X-ray crystallography. The effect of the compounds on cytotoxicity, cell adhesion and migration of the androgen-independent prostate cancer PC-3 cells has been assessed. Compounds 2b and 2c are more cytotoxic than additive doses of titanocene dichloride and free oxime proligand, probing the synergistic effect of these novel compounds. The cytotoxicity of 2b and 2c has been further evaluated against human renal Caki-1, colon DLD-1 and triple negative breast MDA-MB-231 cancer cell lines. The activity found for 2c on PC-3 and Caki-1 is higher than that of highly active Titanocene Y (bis-[(p-methoxybenzyl)cyclopentadienyl]titanium(IV) dichloride), while showing selectivity against renal cancer when compared to a non-tumorigenic human renal (HEK-293T) cell line. Compounds 2b and especially 2c are apoptotic in Caki-1 cancer cell lines. Cell adhesion and wound-healing assays confirmed that derivatives 1c·HCl, 2b and 2c affect the adhesion and migration patterns of the PC-3 cell line. Interactions of the novel compounds with plasmid (pBR322) DNA have also been studied, showing that the oximato Ti(IV) derivatives have a weak or no interaction with DNA at physiological pH.

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Section: Introductionmentioning

confidence: 99%

Novel enantiopure cyclopentadienyl Ti(IV) oximato compounds as potential anticancer agents

Cueva-Alique

Muñoz-Moreno

Benabdelouahab

et al. 2016

Journal of Inorganic Biochemistry

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“…[34–38] Within this context, enantiomerically pure, naturally occurring terpenes are useful building blocks for asymmetric synthesis. [39,40] They are inexpensive starting reagents, commercially available in optically pure form and easily tailored by stereoselective functionalization. [41] Some of us recently published the stereoselective synthesis of ruthenium compounds with amino-oxime ligands derived from R-limonene.…”

Section: Introductionmentioning

confidence: 99%

Hydrogen Bonding and Anticancer Properties of Water‐Soluble Chiral p‐Cymene Ru^II Compounds with Amino‐Oxime Ligands

et al. 2015

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The investigation of the hydrogen-bonding effect on the aggregation tendency of ruthenium compounds [(η6-p-cymene)Ru(κNHR,κNOH)Cl]Cl (R = Ph (1a), Bn (1b)) and [(η6-p-cymene)Ru(κ2NH(2-pic),κNOH)][PF6]2 (1c), [(η6-p-cymene)Ru(κNHBn,κNO)Cl] (2b) and [(η6-p-cymene)Ru(κNBn,κ2NO)] (3b), has been performed by means of concentration dependence 1H NMR chemical shifts and DOSY experiments. The synthesis and full characterization of new compounds 1c, [(η6-p-cymene)Ru(κNPh,κ2NO)] (3a) and 3b are also reported. The effect of the water soluble ruthenium complexes 1a-1c on cytotoxicity, cell adhesion and cell migration of the androgen-independent prostate cancer PC3 cells have been assessed by MTT, adhesion to type-I-collagen and recovery of monolayer wounds assays, respectively. Interactions of 1a-1c with DNA and human serum albumin have also been studied. Altogether, the properties reported herein suggest that ruthenium compounds 1a-1c have considerable potential as anticancer agents against advanced prostate cancer.

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“…2) [62,63], derived from S-limonene. This naturally occurring terpene is an inexpensive starting reagent, commercially available in an optically pure form and easily tailored by stereoselective functionalization [64,65].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Biological evaluation of water soluble arene Ru(II) enantiomers with amino-oxime ligands

Cueva-Alique

Sierra

Muñoz-Moreno

et al. 2018

Journal of Inorganic Biochemistry

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New water soluble, enantiopure arene ruthenium compound SS-(1R,4S)-[(η-p-cymene)Ru{ĸNH(Bn),ĸNOH}Cl]Cl (Bn = benzyl, 1a') has been synthesized. The novel compound along with that previously described RR-(1S,4R)-[(η-p-cymene)Ru{ĸNH(Bn),ĸNOH}Cl]Cl (1a) was evaluated by polarimetry, ultra-violet and circular dichroism spectroscopy. The structure of novel ruthenium derivative 1a' was determined by single crystal X-ray crystallography. Both enantiomers have been tested against several cancer cell lines in vitro: prostate PC-3, lung A-549, pancreas MIA PaCa-2, colorectal HCT-116, leukemia Jurkat and cervical HeLa. Both enantiomers are active and versatile cytotoxic agents, showing IC values from 2 to 12 times lower than those found for cisplatin in the different cell lines evaluated. The mechanism of cell death induced by the metal compounds was analyzed in A-549 and Jurkat cell lines. Derivatives 1a and 1a' induced apoptotic cell death of A-549 cells while dose-dependent cell death mechanisms have been found in the Jurkat cell line. Compound-DNA interactions have been investigated by equilibrium dialysis, Fluorescence Resonance Energy Transfer (FRET) melting assays and viscometric titrations, revealing moderate binding affinity of 1a and 1a' towards duplex DNA. Finally, the efficacy of 1a in a preliminary in vivo assay of PC-3 xenografts in nude mice has been evaluated, resulting in a promising inhibition of tumor growth by 45%. Analysis of tumor tissue also showed a significant decrease of levels of crucial molecules in the invasive phenotype of PC-3 cells.

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Metal complexes with new types of chiral ligands based on natural terpenes

Cited by 28 publications

References 46 publications

Novel enantiopure cyclopentadienyl Ti(IV) oximato compounds as potential anticancer agents

Novel enantiopure cyclopentadienyl Ti(IV) oximato compounds as potential anticancer agents

Hydrogen Bonding and Anticancer Properties of Water‐Soluble Chiral p‐Cymene Ru^II Compounds with Amino‐Oxime Ligands

Biological evaluation of water soluble arene Ru(II) enantiomers with amino-oxime ligands

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Metal complexes with new types of chiral ligands based on natural terpenes

Cited by 28 publications

References 46 publications

Novel enantiopure cyclopentadienyl Ti(IV) oximato compounds as potential anticancer agents

Novel enantiopure cyclopentadienyl Ti(IV) oximato compounds as potential anticancer agents

Hydrogen Bonding and Anticancer Properties of Water‐Soluble Chiral p‐Cymene RuII Compounds with Amino‐Oxime Ligands

Biological evaluation of water soluble arene Ru(II) enantiomers with amino-oxime ligands

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Hydrogen Bonding and Anticancer Properties of Water‐Soluble Chiral p‐Cymene Ru^II Compounds with Amino‐Oxime Ligands