4335-90-4Relevant academic research and scientific papers
Investigation of in vitro anticancer and DNA strap interactions in live cells using carboplatin type Cu(II) and Zn(II) metalloinsertors
Pravin, Narayanaperumal,Raman, Natarajan
, p. 675 - 687 (2014)
A series of carboplatin type Cu(II) and Zn(II) metalloinsertors (1-8) having β-diketone analogues and biologically significant cyclobutane-1,1-dicarboxylic acid have been synthesized and characterized by spectral and analytical methods. The binding and cleavage propensity of these metalloinsertors on DNA and their cytotoxic effects in live cells have been explored. From the gel electrophoresis study, it is observed that the complexes 1-8 cleave pBR322 DNA via a hydrolytic mechanism induced by hydroxyl radical scavengers, DMSO and EtOH as the reactive oxygen species (ROS). In vivo antitumor efficacy has been studied on EAC tumor bearing mice which is assessed by mean survival time, effect on hematological parameters and solid tumor volume. The results strongly support that complex 1 shows potent antitumor effect against EAC and higher than the standard drug carboplatin. Moreover, the cytotoxicity of the complexes, screened on a panel of human cancerous cell lines viz., human cervical cancer cells (HeLa), human breast adenocarcinoma cells (MCF-7), human laryngeal epithelial carcinoma cells (HEp-2), human liver carcinoma cells (Hep G2) and non-cancerous NIH 3T3 mouse embryonic fibroblasts cell lines, reveals that complex 1 exhibits a better anticancer activity than other complexes and standards.
Lasing the DNA fragments through β-diketimine framed Knoevenagel condensed Cu(II) and Zn(II) complexes - An in vitro and in vivo approach
Raman, Natarajan,Pravin, Narayanaperumal
, p. 867 - 882 (2014)
The syntheses, structures and spectroscopic properties of Cu(II) and Zn(II) complexes having Knoevenagel condensate β-diketimine Schiff base ligands have been investigated in this paper. Characterization of these complexes was carried out using FTIR, NMR, UV-Vis, elemental analysis, mass and EPR techniques. Absorption titration, electrochemical analyses and viscosity measurements have also been carried out to determine the mode of binding. The shift in ΔEp, E1/2 and Ipc values explores the interaction of CT DNA with the above metal complexes. Interaction of ligands and their complexes with DNA revealed an intercalative mode of binding between them. Antimicrobial studies showed an effective antimicrobial activity of the metal ions after coordination with the ligands. The antioxidant properties of the Schiff base ligands and their complexes were evaluated in a series of in vitro tests by using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and H 2O2 free radical scavengers. In vivo and in vitro antitumor functions of the complexes against Ehrlich ascites carcinoma tumor model have also been investigated. All the results support that β-diketone derived Knoevenagel condensate Schiff base complexes may act as novel antitumor drugs and suggest that their potent cell life inhibition may contribute to their anti-cancer efficacy.
Mechanism and free energy profile of base-catalyzed Knoevenagel condensation reaction
Dalessandro, Ellen V.,Collin, Hugo P.,Valle, Marcelo S.,Pliego, Josefredo R.
, p. 57803 - 57810 (2016)
The Knoevenagel condensation reaction is a classical method for carbon-carbon bond formation. This reaction can be catalyzed by homogeneous or heterogeneous bases, and in the past ten years many different solid bases catalysts have been investigated. In this report, we have done a reliable theoretical analysis of the reaction mechanism and free energy profile of acetylacetone reaction with benzaldehyde catalyzed by methoxide ion in methanol solution. The analysis was extended for solventless conditions and solid base catalysis. We have found that the enolate addition to the benzaldehyde is a rapid step, contrary to general assumptions on the mechanism. The rate-determining step is the leaving of the hydroxide ion from the anionic intermediate, with a predicted overall free energy barrier of 28.8 kcal mol-1. This finding explains the experimental observation that more polar medium favor the reaction, once the transition state is product-like and involves the formation of the highly solvated hydroxide ion. The present results provides useful insights on this reaction system.
Effective DNA binding and cleaving tendencies of malonic acid coupled transition metal complexes
Pravin, Narayanaperumal,Utthra, Ponnukalai Ponya,Kumaravel, Ganesan,Raman, Natarajan
, p. 162 - 170 (2016)
Eight transition metal complexes were designed to achieve maximum biological efficacy. They were characterized by elemental analysis and various other spectroscopic techniques. The monomeric complexes were found to espouse octahedral geometry and non-electrolytic nature. The DNA interaction propensity of the complexes with calf thymus DNA (CT-DNA), studied at physiological pH by spectrophotometric, spectrofluorometric, cyclic voltammetry, and viscometric techniques revealed intercalation as the possible binding mode. Fascinatingly, the complexes were found to exhibit greater binding strength than that of the free ligands. A strong hypochromism and a slight red shift were exhibited by complex 5 among the other complexes. The intrinsic binding constant values of all the complexes compared to cisplatin reveal that they are excellent metallonucleases than that of cisplatin. The complexes were also shown to reveal displacement of the ethidium bromide, a strong intercalator using fluorescence titrations. Gel electrophoresis was used to divulge the competence of the complexes in cleaving the supercoiled pBR322 plasmid DNA. From the results, it is concluded that the complexes, especially 5, are excellent chemical nucleases in the presence of H2O2. Furthermore, the in vitro antimicrobial screening of the complexes exposes that these complexes are excellent antimicrobial agents. Overall the effect of coligands is evident from the results of all the investigations.
Novel diketone compound
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Paragraph 0059; 0064; 0067-0069; 0262-0268, (2021/04/28)
The invention relates to a novel diketone compound. The compounds are compounds of Formula I and pharmaceutically acceptable salts, prodrugs and solvates thereof, as well as pharmaceutical compositions comprising the compounds, and methods of synthesis thereof are provided. Furthermore, the present invention relates to pharmaceutical compositions comprising said compounds, which can be used to inhibit the activity of tumor-associated target proteins or genes.
Reductive Knoevenagel Condensation with the Zn-AcOH System
Ivanov, Konstantin L.,Melnikov, Mikhail Ya.,Budynina, Ekaterina M.
, p. 1285 - 1291 (2020/11/13)
An efficient gram-scale one-pot approach to 2-substituted malonates and related structures is developed, starting from commercially available aldehydes and active methylene compounds. The technique combines Knoevenagel condensation with the reduction of the C=C bond in the resulting activated alkenes with the Zn-AcOH system. The relative ease with which the C=C bond reduction occurs can be traced to the accepting abilities of the substituents in the intermediate arylidene malonates.
Efficient and recyclable solid acid-catalyzed alkylation of active methylene compound via oxonium intermediate for atom economical synthesis of organic compounds
Naikwadi, Dhanaji R.,Bankar, Balasaheb D.,Ravi, Krishnan,Biradar, Ankush V.
, p. 3691 - 3703 (2021/06/12)
In the present work, we report the catalytic reaction of active methylene compounds with cyclic enol ethers and aryl acetals through oxonium intermediate under solvent-free conditions using heterogeneous solid acid catalysts. Among studied solid acid catalysts, Amberlyst-15 gave excellent yields (35–85%) of alkylated products. The catalyst showed broader substrate scope, and a recyclable catalytic cost-efficient approach of the alkylation was examined on the different types of cyclic enol ethers and aryl acetal.
Lewis Acid and Base Catalysis of YNbO4 Toward Aqueous-Phase Conversion of Hexose and Triose Sugars to Lactic Acid in Water
Kim, Minjune,Ronchetti, Silvia,Onida, Barbara,Ichikuni, Nobuyuki,Fukuoka, Atsushi,Kato, Hideki,Nakajima, Kiyotaka
, p. 350 - 359 (2019/11/14)
Amphoteric YNbO4 was synthesized by the simple coprecipitation using (NH4)3[Nb(O2)4] and Y(NO3)3, and examined as a new solid acid-base bifunctional catalyst for various reactions including aqueous-phase conversion of glucose to lactic acid. After drying the white precipitate at 353 K for 3 h, the resultant oxide is an amorphous YNbO4 with high densities of Lewis acid sites (0.18 mmol g?1) and base sites (0.38 mmol g?1). Negatively-charged lattice oxygen of amorphous YNbO4 functioned as Lewis base sites that promote a Claisen-Schmidt-type condensation reaction with acetylacetone and benzaldehyde with comparable activity to reference catalysts. Amorphous YNbO4 can also be applicable to the production of lactic acid from glucose in water, which gives relatively high yields (19.6 %) compared with other reference catalysts. Mechanistic studies using glucose-1-d and 2H nuclear magnetic resonance spectroscopy (NMR) revealed that YNbO4 first converts glucose to two carbohydrates (glyceraldehyde and pyruvaldehyde) through dehydration via the formation of 3-deoxyglucosone and subsequent retro-aldolization, and these intermediates are then converted to lactic acid by both dehydration and isomerization through hydride transfer.
Iodine/water-mediated deprotective oxidation of allylic ethers to access α,β-unsaturated ketones and aldehydes
Chen, Weifeng,Jiang, Kezhi,Xue, Yuntian,Yan, Yaolong,Yang, Lei
, p. 14720 - 14724 (2020/04/27)
The first iodine/water-mediated deprotective oxidation of allylic ethers to access α,β-unsaturated ketones and aldehydes was achieved. The reaction tolerates a wide range of functionalities. Furthermore, this protocol was found to be applicable to the oxidative transformation of allylic acetates. The proposed mechanism involves an oxygen transfer from solvent water to the carbonyl products.
Cross-linked polystyrene-TiCl4 complex as a reusable Lewis acid catalyst for solvent-free Knoevenagel condensations of 1,3-dicarbonyl compounds with aldehydes
Rahmatpour, Ali,Goodarzi, Niloofar
, p. 24 - 31 (2019/03/08)
Cross-linked polystyrene copolymer beads with the average particle size in the range of (50–80 mesh size) were prepared by a new method, characterized and functionalized with titanium tetrachloride to afford the corresponding polystyrene?titanium tetrachloride complex in one step reaction and characterized by FT-IR, UV, TGA, DSC, XRD, SEM, BET. This polymer metal complex (PS/TiCl4) was used as a heterogeneous, recoverable, reusable Lewis acid for solvent-free Knoevenagel condensations of 1,3-diketones with aromatic aldehydes under green and mild conditions. The rate of reactions was found to decrease with an increasing percentage of crosslinking and the mesh size of the copolymer beads. This complex showed good stability and catalytic activity in the Knoevenagel reactions.
