Browse
Submit Data
Databases
API
Help

Dataset Information

20 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Metal-free domino amination-Knoevenagel condensation approach to access new coumarins as potent nanomolar inhibitors of VEGFR-2 and EGFR

ABSTRACT: A metal-free, atom-economy and simple work-up domino amination-Knoevenagel condensation approach to construct new coumarin analogous (4a-f and 8a-e) was described. Further, new formyl (5a,d-f) and nitro (9a,d-f) coumarin derivatives were synthesized via C-N coupling reaction of various cyclic secondary amines and 4-chloro-3-(formyl-/nitro)coumarins (1a,c), respectively. The confirmed compounds were screened for their in vitro anti-proliferative activity against KB-3-1, A549 and PC3 human cancer cell lines using resazurin cellular-based assay. Among them, coumarin derivatives 4e and 8e displayed the best anti-cervical cancer potency (KB-3-1) with IC50 values of 15.5 ± 3.54 and 21 ± 4.24 μM, respectively. Also, 4e showed the most promising cytotoxicity toward A549 with IC50 value of 12.94 ± 1.51 μM. As well, 9d presented a more significant impact of potency against PC3 with IC50 7.31 ± 0.48 μM. Moreover, 8d manifested selectivity against PC3 (IC50 = 20.16 ± 0.07 μM), while 8e was selective toward KB-3-1 cell line (IC50 = 21 ± 4.24 μM). Matching with docking profile, the enzymatic assay divulged that 8e is a dual potent single-digit nanomolar inhibitor of VEGFR-2 and EGFR with IC50 values of 24.67 nM and 31.6 nM that were almost equipotent to sorafenib (31.08 nM) and erlotinib (26.79 nM), respectively. Graphical Abstract

SUBMITTER: Eliwa E

PROVIDER: S-EPMC9273165 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

An intramolecular relay catalysis strategy for Knoevenagel condensation and 1,3-dipolar cycloaddition domino reactions.

Project description:A relay catalysis strategy was established by using a bifunctional catalyst which was prepared by immobilization of organic chains containing secondary amine and Cu(ii) complex onto silica-coated nano-Fe3O4. The simply prepared nanoparticles acted as efficient, intramolecular relays and magnetically recyclable base-metal bifunctional catalysts for Knoevenagel condensation and 1,3-dipolar cycloaddition domino reactions to prepare 5-substituted 1H-tetrazoles with excellent yields.

| S-EPMC9073340 | biostudies-literature

Mechanochemical Knoevenagel condensation investigated in situ.

Project description:The mechanochemical Knoevenagel condensation of malononitrile with p-nitrobenzaldehyde was studied in situ using a tandem approach. X-ray diffraction and Raman spectroscopy were combined to yield time-resolved information on the milling process. Under solvent-free conditions, the reaction leads to a quantitative conversion to p-nitrobenzylidenemalononitrile within 50 minutes. The in situ data indicate that the process is fast and proceeds under a direct conversion. After stopping the milling process, the reaction continues until complete conversion. The continuous and the stopped milling process both result in crystalline products suitable for single crystal X-ray diffraction.

| S-EPMC5629385 | biostudies-literature

Sustainable Synthesis of <i>p</i>-Hydroxycinnamic Diacids through Proline-Mediated Knoevenagel Condensation in Ethanol: An Access to Potent Phenolic UV Filters and Radical Scavengers.

Project description:p-Hydroxycinnamic diacids are reaction intermediates of the classical Knoevenagel-Doebner condensation between malonic acid and benzaldehydes. As they are generally obtained in low yields, they remain relatively under-studied and under-exploited. Herein, we developed and optimized a sustainable synthetic procedure allowing the production of these compounds in good to high yields (60-80%) using proline as the catalyst and ethanol as the solvent. Study of their antioxidant and anti-UV activities revealed that these p-hydroxycinnamic diacids were not only potent radical scavengers but also efficient UV filters exhibiting high photostability.

| S-EPMC7222392 | biostudies-literature

Total synthesis of flocoumafen via knoevenagel condensation and intramolecular ring cyclization: general access to natural products.

Project description:The total synthesis and structure determination of cis- and trans-flocoumafen was described. The key synthetic steps involve Knoevenagel condensation with p-methoxybenzaldehyde, in situ decarboxylation and intramolecular ring cyclization to construct the tetralone skeleton. Stereospecific reduction of the O-alkylated ketone 13 afforded good yield of precusor alcohol 5. Final coupling of alcohol 5 with 4-hydroxy-coumarin yielded flocoumafen (1). Separation and structure determination of cis- and trans-flocoumafen through 2D NMR analyses-assisted computer simulation techniques for the evaluation of anticoagulant activities are reported for the first time. This method is useful for generating the core tetralone skeleton of 4-hydroxycoumarin derivatives and provides a generalized access to various warfarin type anticoagulants.

| S-EPMC6268178 | biostudies-literature

Unexpected polymorphism during a catalyzed mechanochemical Knoevenagel condensation.

Project description:The transformation of a base-catalyzed, mechano-assisted Knoevenagel condensation of mono-fluorinated benzaldehyde derivatives (p-, m-, o-benzaldehyde) with malonodinitrile was investigated in situ and in real time. Upon milling, the para-substituted product was found to crystallize initially into two different polymorphic forms, depending on the quantity of catalyst used. For low catalyst concentrations, a mechanically metastable phase (monoclinic) was initially formed, converting to the mechanically stable phase (triclinic) upon further grinding. Instead, higher catalyst concentrations crystallize directly as the triclinic product. Inclusion of catalyst in the final product, as evidenced by mass spectrometric analysis, suggests this complex polymorphic pathway may be due to seeding effects. Multivariate analysis for the in situ Raman spectra supports this complex formation pathway, and offers a new approach to monitoring multi-phase reactions during ball milling.

| S-EPMC6541349 | biostudies-literature

Pickering Interfacial Catalysis-Knoevenagel Condensation in Magnesium Oxide-Stabilized Pickering Emulsion.

Project description:In the present study, a novel catalytic route for the Knoevenagel condensation reaction has been developed by Pickering interfacial catalysis using magnesium oxide (MgO) as both an emulsion stabilizer and a base catalyst. MgO was prepared by the precipitation method using sodium hydroxide or ammonium hydroxide as the precipitating agent and calcined at different temperatures. The calcined samples were characterized by XRD, SEM, TEM, AFM, BET, and DLS techniques. The catalytic application of the emulsions stabilized by MgO was investigated for the Knoevenagel condensation reaction of benzaldehyde and its derivatives with malononitrile. All of the reactions were carried out at an ambient temperature (30 °C) under static conditions without stirring. Both the emulsion-stabilizing ability and the catalytic activity of MgO were found to be affected by the method of preparation, calcination temperature, and the nature of the oil phase. It was observed that the method of preparation varied the texture and morphology of MgO and thus the stability and droplet size of the emulsion formed. This was further reflected in the catalytic activity. The highest yield (87%) of the condensation product was obtained with MgO prepared by precipitation using a strong base (NaOH) and further calcined at 400 °C. The developed catalytic system offers several green chemistry advantages such as reusable solid-base catalyst and use of a single material as both emulsion stabilizer and catalyst. Room-temperature reaction under static conditions is an additional advantage of the developed catalytic system.

| S-EPMC7271354 | biostudies-literature

On-Surface Formation of Cyano-Vinylene Linked Chains by Knoevenagel Condensation.

Project description:The rapid development of on-surface synthesis provides a unique approach toward the formation of carbon-based nanostructures with designed properties. Herein, we present the on-surface formation of CN-substituted phenylene vinylene chains on the Au(111) surface, thermally induced by annealing the substrate stepwise at temperatures between 220 °C and 240 °C. The reaction is investigated by scanning tunneling microscopy and density functional theory. Supported by the calculated reaction pathway, we assign the observed chain formation to a Knoevenagel condensation between an aldehyde and a methylene nitrile substituent.

| S-EPMC9298206 | biostudies-literature

Facile access to potent antiviral quinazoline heterocycles with fluorescence properties via merging metal-free domino reactions.

Project description:Most of the known approved drugs comprise functionalized heterocyclic compounds as subunits. Among them, non-fluorescent quinazolines with four different substitution patterns are found in a variety of clinically used pharmaceuticals, while 4,5,7,8-substituted quinazolines and those displaying their own specific fluorescence, favourable for cellular uptake visualization, have not been described so far. Here we report the development of a one-pot synthetic strategy to access these 4,5,7,8-substituted quinazolines, which are fluorescent and feature strong antiviral properties (EC50 down to 0.6±0.1 μM) against human cytomegalovirus (HCMV). Merging multistep domino processes in one-pot under fully metal-free conditions leads to sustainable, maximum efficient and high-yielding organic synthesis. Furthermore, generation of artesunic acid-quinazoline hybrids and their application against HCMV (EC50 down to 0.1±0.0 μM) is demonstrated. Fluorescence of new antiviral hybrids and quinazolines has potential applications in molecular imaging in drug development and mechanistic studies, avoiding requirement of linkage to external fluorescent markers.

| S-EPMC5418574 | biostudies-literature

Kinetics Studies on a Multicomponent Knoevenagel-Michael Domino Reaction by an Automated Flow Reactor.

Project description:The optimization of complex chemical reaction systems is often a troublesome and time-consuming process. The application of modern technologies, including automated reactors and analytics, opens the avenue for generating large data sets on chemical reaction processes in a short period of time. In this work, an automated flow reactor is used to present detailed kinetics and mechanistic studies about an amine-catalyzed Knoevenagel-Michael domino reaction to yield tetrahydrochromene derivatives. High-performance monoliths as catalyst supports and online coupled HPLC analysis allow for time-efficient data generation. We show that the two-step multicomponent domino reaction does not follow the kinetics of consecutive reaction steps proceeding independently from each other. Instead, the starting materials of both individual reactions compete for the active sites on the heterogeneous catalyst, which lowers the rate constants of both steps. This knowledge was used to implement a more efficient experimental setup which increased the turnover numbers of the catalyst, without adjusting common reaction parameters like temperature, reaction time, and concentrations.

| S-EPMC6511915 | biostudies-literature

Intercepted-Knoevenagel condensation for the synthesis of unsymmetrical fused-tricyclic 4H-pyrans.

Project description:4H-Pyrans (4H-Pys) and 1,4-dihydropyridines (1,4-DHPs) are important classes of heterocyclic scaffolds in medicinal chemistry. Herein, an indium(III)-catalyzed one-pot domino reaction for the synthesis of highly functionalized 4H-Pys, and a model of 1,4-DHP is reported. This alternative approach to the challenging Hantzsch 4-component reaction enables the synthesis of fused-tricyclic heterocycles, and the mechanistic studies underline the importance of an intercepted-Knoevenagel adduct to achieve higher chemoselectivity towards these types of unsymmetrical heterocycles.

| S-EPMC6859900 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data