853649-55-5

Upstream product

• 91026-00-5 N-benzyl-2,3-dibromo-maleimide 
• 16114-24-2 1-benzyl-3,4-dichloro-pyrrole-2,5-dione 
• 100-46-9 benzylamine 

Downstream Products

• 853649-33-9 3,4-bis[5-(diethoxymethyl)fur-2-yl]-2,5-dihydro-1-benzyl-1H-pyrrole-2,5-dione 

Relevant academic research and scientific papers

An acyclic enediyne anticancer compound attributed to a Bergman cyclization at physiological temperature

Enediyne cytotoxic drugs have attracted much attention because of their unique structure and potent anticancer activity. However, acyclic enediynes are long considered as inactive at physiological temperature due to their long C1-C6 distance. By adjusting the steric bulkiness of the functional groups at the alkynyl termini and the electron-withdrawing effect at the ene moiety, herein, a simple acyclic enediyne was designed and synthesized to achieve the onset of thermal Bergman cyclization at physiological temperature in polar solvents. The spontaneous generation of diradical intermediates was confirmed through EPR analysis and further supported by spin trapping experiment, radical indicator experiment, and high resolution MS analysis. The reactive diradicals generated in aqueous media induced single and double stranded cleavage of DNA, and showed high cytotoxicity to Hela cells. The IC50 value of the enediyne compound is comparable to many clinical used anti-tumor agents.

Preparation and antitumor applications of asymmetric propargyl amide maleimide based enediyne antibiotics

Maleimide-based enediynes with propargyl amide at one arm and other kinds of alkyne at the other arm were synthesized via Sonogashira reaction. The logP values of these enediyne antibiotics were adjusted by changing the alkyl chain length and installing a hydroxyl group. As confirmed by electron paramagnetic resonance analysis, the enediynes generated reactive free radicals at physiological temperature, which endows them the ability to cause DNA cleavage and lead to tumor cell death. While most of the enediynes act in small molecular form, one of them showed amphiphilic property and formed vesicles in deionized water for potential self-delivery applications. The reactive oxygen species level in tumor cells was enhanced in the presence of these enediynes, leading to cell death through apoptosis pathway. The half inhibition concentrations (IC50) of the enediynes towards HeLa cells were on the micromolar level, comparable to many commercial anticancer agents.

Self-Delivery Nanoparticles of Amphiphilic Acyclic Enediynes for Efficient Tumor Cell Suppression

Four acyclic maleimide-based enediyne compounds with different hydrophilicity were synthesized through Sonogashira reaction to reveal a self-delivery antitumor drug platform. As proved by ESR analysis, the enediyne compounds undergo Bergman-like cyclization and generate diradical intermediates at physiological temperature, which are able to induce DNA-cleavage through the abstraction of H atoms from the sugar-phosphate backbones. When the critical aggregation concentration is reached in water, the amphiphilic enediyne compounds self-assemble into nanoparticles and possess the self-delivery ability to be facilely admitted by tumor cells, resulting in greatly improved cytotoxicity (IC50 down to 10 μmol·L–1) and much higher tumor cell apoptosis rate (up to 86.6%) in comparison with either the hydrophilic or the lipophilic enediyne compound. The enhanced endocytosis of the amphiphilic enediyne compounds was further confirmed through confocal laser scanning microscopy analysis. The unveiled relationship between the hydrophilicity of enediyne drugs and their therapeutic efficacy will provide a guideline for the design of new self-delivery drugs employed in medicinal applications.

Coordination-Accelerated Radical Formation from Acyclic Enediynes for Tumor Cell Suppression

A maleimide-based acyclic enediyne with salicylaldiminato substituents at the alkyne termini was synthesized, which was further chelated with three kinds of metal-ions, CuII, ZnII, and MgII, and form metalloenediynes. The cycloaromatization of this thermally inactive enediyne ligand was greatly accelerated through the coordination with metal ions. Specifically, the CuII-metalloenediyne showed an extremely low onset temperature of 55 °C and underwent spontaneous cycloaromatization at ambient temperature to produce free radicals, followed by generation of reactive oxygen species in the physiological environment. The metalloenediyne exhibited excellent DNA cleavage ability and high cytotoxicity towards HeLa cells, with half-maximal inhibitory concentration values comparable to many commercial antitumor agents. The combination of the electron-withdrawing effect of the maleimide moiety at the ene position and metal coordination at the yne termini provides a new inspiration for designing and synthesizing highly efficient enediyne antitumor agents.

Maleimide-based acyclic enediyne for efficient DNA-cleavage and tumor cell suppression

A pH-sensitive acyclic enediyne (1) was synthesized for efficient DNA-cleavage and tumor cell suppression. Unlike other acyclic enediynes, this novel enediyne transforms into a highly reactive enediyne (2) in an acidic environment only, which undergoes Be

Synthesis of substituted bis(heteroaryl)maleimides

Substituted bis(fur-2-yl), bis(fur-3-yl) and bis(thien-2-yl) maleimides with potential antidiabetic properties are described. Their synthesis involves, as a key step, a Suzuki cross-coupling between various boron derivatives and the diiodomaleimides. Therefore, a wide range of substituted symmetric and non-symmetric maleimide derivatives can be prepared.