Synthesis and biological evaluation of novel imidazole-containing macrocycles

Nshimyumukiza, Prosper; Berge, Emilie Van Den; Delest, Bruno; Mijatovic, Tatjana; Kiss, Róbert; Marchand‐Brynaert, Jacqueline; Robiette, Raphaël

doi:10.1016/j.tet.2010.04.070

Cited by 21 publications

(23 citation statements)

References 23 publications

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“…The synthesis of macrocycles 1a and 1c has already been reported 6. In order to investigate the influence of the size of the macrocycle, we have synthesized imidazoles 1b and 1d using the same strategy (Scheme ).…”

Section: Resultsmentioning

confidence: 99%

“…In a previous study,6 we found that 1a and 1c display potent binding activity towards three biological targets, which are important actors in the central nervous system: A 3 adenosine (h) receptor, dopamine D 1 (h) receptor and chlorine channel (GABA‐gated). In order to investigate the importance of chirality on these biological activities, we submitted the two optically pure enantiomers of 1a as well as 1b – d to the same biological tests.…”

Section: Resultsmentioning

confidence: 99%

“…In this context, we have recently designed and synthesized a new family of compounds comprising a 5‐aryl‐1 H ‐imidazole motif included in a macrocycle (Scheme ) 6. Biological evaluation of these imidazole‐containing macrocycles revealed that they display interesting binding activities towards biological targets, which are important factors in the central nervous system: A 3 adenosine (h) receptor, dopamine D 1 (h) receptor and chlorine channel (GABA‐gated).…”

Section: Introductionmentioning

confidence: 99%

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Planar Chirality of Imidazole‐Containing Macrocycles – Understanding and Tuning Atropisomerism

et al. 2011

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The synthesis and characterization of imidazole-containing macrocycles displaying planar chirality has been achieved. HLPC and NMR studies revealed the crucial role of the alicyclic chain length in determining the rate of stereoisomerisation: 15-and 16-membered cyclic compounds are chiral whereas their larger-ringed analogues equilibrate rapidly at room temperature. Computational calculations are in good

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Planar Chirality of Imidazole‐Containing Macrocycles – Understanding and Tuning Atropisomerism

et al. 2011

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“…For example, the imidazole macrocyclic scaffold of general structure 65 ( Figure 11.9) was synthesized via RCM and found to display a range of potentially interesting binding activities for adenosine and dopamine receptors, ion channels and transporters. 159 A series of bicyclic 1,3-bridged-2-azetidinones (66 as a representative structure), which have been demonstrated to be inhibitors of penicillin-binding proteins, represents another novel macrocyclic structural class accessed by RCM methodology. [160][161][162] Interestingly, both monomer and dimer-derived structures obtained from these latter efforts have been found to have utility.…”

Section: Ring-closing Metathesismentioning

confidence: 99%

The Synthesis of Macrocycles for Drug Discovery

Peterson¹

2014

Macrocycles in Drug Discovery

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Despite the attractive nature of macrocyclic compounds for use in new pharmaceutical discovery, applications have been hindered due to the lack of appropriate synthetic methods, in particular for the construction of libraries of such molecules. However, over the last decade, a number of effective and versatile methodologies suitable for macrocyclic scaffolds have been developed and applied successfully. These include classical coupling and substitution reactions, ring-closing metathesis (RCM), cycloaddition (“click”) chemistry, multicomponent reactions (MCR), numerous organometallic-mediated processes and others. This chapter presents a comprehensive compilation of these strategies and provides examples of their use in drug discovery, along with a description of those approaches that have proven effective for the assembly of macrocyclic libraries suitable for screening.

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“…They exhibit different biological activities such as nitric-oxide synthase inhibition, anti-inflammatory, anti-parasitic, antifungal, antidepressant, antitubercular, anticancer and antiviral activities [4][5][6][7][8][9][10][11]. Hence, imidazole moiety is found in numerous drugs, such as anti-inflammatory agents, kinase inhibitors, antagonists of CB1 cannabinoid and glucagon receptors and antibacterial agents [12].…”

Section: Introductionmentioning

confidence: 99%

DNA Interaction Studies and In Vitro Cytotoxicity of Newly Synthesized Steroidal Imidazolidinones

et al. 2015

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New steroidal imidazolidinone derivatives (7-9) were synthesized after reacting steroidal thiosemicarbazones with oxalyl chloride in absolute ethanol. After characterization by spectral and analytical data, the interaction studies of compounds (7-9) with DNA were carried out by UV-vis, fluorescence spectroscopy, circular dichroism, molecular docking and gel electrophoresis. The compounds bind to DNA preferentially through electrostatic and hydrophobic interactions with Kb; 2.31 × 10(4) M(-1), 2.57 × 10(4) M(-1) and 2.16 × 10(4) M(-1), respectively indicating the higher binding affinity of compound 8 towards DNA. Gel electrophoresis demonstrated that the compounds 7-9 show strong interaction during the cleavage activity with pBR322 DNA. The docking study suggested the intercalation of imidazolidinone moiety of steroid derivative in minor groove of DNA. During in vitro cytotoxicity, compounds 7-9 revealed potential toxicity against the different human cancer cells (MTT assay). Apoptotic degradation of DNA in presence of compounds 7-9 was analyzed by agarose gel electrophoresis and visualized by ethidium bromide staining (comet assay). FACS analysis shows that the compound 8 bring about cell cycle arrest at 7 μM concentration.

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Synthesis and biological evaluation of novel imidazole-containing macrocycles

Cited by 21 publications

References 23 publications

Planar Chirality of Imidazole‐Containing Macrocycles – Understanding and Tuning Atropisomerism

Planar Chirality of Imidazole‐Containing Macrocycles – Understanding and Tuning Atropisomerism

The Synthesis of Macrocycles for Drug Discovery

DNA Interaction Studies and In Vitro Cytotoxicity of Newly Synthesized Steroidal Imidazolidinones

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