Design, synthesis and biological evaluation of 4-chromanone derivatives as IKr inhibitors

Wang, Rong; Liu, Zhenzhen; Du, Lüpei; Li, Minyong

doi:10.5582/ddt.8.76

Cited by 4 publications

(2 citation statements)

References 20 publications

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“…Chromanones synthesized or extracted from diverse sources have previously been assessed and shown to exhibit diverse pharmacological functions [including antimicrobial ( Xu et al, 1998 ; Kanokmedhakul et al, 2002 ; Cottiglia et al, 2004 ; do Nascimento et al, 2007 ; Tanaka et al, 2009 ), anti-oxidant ( Lee et al, 2005 ) and anti-inflammatory effects ( Konieczny et al, 1976 ), as well as effects on cardiac muscle repolarization ( Wang et al, 2014 ) and coronary artery vasodilation ( Nagao et al, 1972 )]. This diversity of pharmacological activity supports our cell-cycle data which may suggest divergent mechanisms of action for brasiliensic and isobrasiliensic acids at higher doses.…”

Section: Discussionmentioning

confidence: 99%

Hexane Extracts of Calophyllum brasiliense Inhibit the Development of Gastric Preneoplasia in Helicobacter felis Infected INS-Gas Mice

et al. 2017

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Objectives: Indigenous Latin American populations have used extracts from Calophyllum brasiliense, a native hardwood, to treat gastrointestinal symptoms for generations. The hexane extract of Calophyllum brasiliense stem bark (HECb) protects against ethanol-mediated gastric ulceration in Swiss–Webster mice. We investigated whether HECb inhibits the development of gastric epithelial pathology following Helicobacter felis infection of INS-Gas mice.Materials and Methods: Groups of five male, 6-week-old INS-Gas mice were colonized with H. felis by gavage. From 2 weeks after colonization their drinking water was supplemented with 2% Tween20 (vehicle), low dose HECb (33 mg/L, lHECb) or high dose HECb (133 mg/L, hHECb). Equivalent uninfected groups were studied. Animals were culled 6 weeks after H. felis colonization. Preneoplastic pathology was quantified using established histological criteria. Gastric epithelial cell turnover was quantified by immunohistochemistry for Ki67 and active-caspase 3. Cytokines were quantified using an electrochemiluminescence assay.Results: Vehicle-treated H. felis infected mice exhibited higher gastric atrophy scores than similarly treated uninfected mice (mean atrophy score 5.6 ± 0.87 SEM vs. 2.2 ± 0.58, p < 0.01). The same pattern was observed following lHECb. Following hHECb treatment, H. felis status did not significantly alter atrophy scores. Gastric epithelial apoptosis was not altered by H. felis or HECb administration. Amongst vehicle-treated mice, gastric epithelial cell proliferation was increased 2.8-fold in infected compared to uninfected animals (p < 0.01). Administration of either lHECb or hHECb reduced proliferation in infected mice to levels similar to uninfected mice. A Th17 polarized response to H. felis infection was observed in all infected groups. hHECb attenuated IFN-γ, IL-6, and TNF production following H. felis infection [70% (p < 0.01), 67% (p < 0.01), and 41% (p < 0.05) reduction vs. vehicle, respectively].Conclusion: HECb modulates gastric epithelial pathology following H. felis infection of INS-Gas mice. Further studies are indicated to confirm the mechanisms underlying these observations.

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Section: Discussionmentioning

confidence: 99%

Hexane Extracts of Calophyllum brasiliense Inhibit the Development of Gastric Preneoplasia in Helicobacter felis Infected INS-Gas Mice

et al. 2017

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“…Furthermore, we will also address recent reports focusing on new druggable targets and novel pharmacological activities. Nevertheless, it is important to acknowledge recent reports on the cardiovascular application of chromones and chromanones, mainly as vasorelaxants and in repolarization of cardiac tissue, in retinal neovascularization, and as alkaline phosphatase inhibitors. , …”

Section: Biological Interest Of Chromonesmentioning

confidence: 99%

Chromone as a Privileged Scaffold in Drug Discovery: Recent Advances

et al. 2017

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The use of privileged structures in drug discovery has proven to be an effective strategy, allowing the generation of innovative hits/leads and successful optimization processes. Chromone is recognized as a privileged structure and a useful template for the design of novel compounds with potential pharmacological interest, particularly in the field of neurodegenerative, inflammatory, and infectious diseases as well as diabetes and cancer. This perspective provides the reader with an update of an earlier article entitled "Chromone: A Valid Scaffold in Medicinal Chemistry" ( Chem. Rev. 2014 , 114 , 4960 - 4992 ) and is mainly focused on chromones of biological interest, including those isolated from natural sources. Moreover, as drug repurposing is becoming an attractive drug discovery approach, recent repurposing studies of chromone-based drugs are also reported.

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Suzuki–Miyaura Cross‐Coupling Reactions of Tetrahydroxanthones and 4‐Chromanone Lactones to Heteromeric Biaryls

2017

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We are reporting on a Suzuki–Miyaura cross‐coupling study of a tetrahydroxanthone model system with different boronic acids, pinacolboranes, and halides to afford heteromeric biaryls. We transferred these reaction conditions to the Suzuki–Miyaura cross‐coupling reactions of 4‐chromanone lactones. We thereby obtained complex building blocks offering a convenient starting point for further transformations towards various natural products with the tetrahydroxanthone structural motif.magnified image

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Design, synthesis and biological evaluation of 4-chromanone derivatives as IKr inhibitors

Cited by 4 publications

References 20 publications

Hexane Extracts of Calophyllum brasiliense Inhibit the Development of Gastric Preneoplasia in Helicobacter felis Infected INS-Gas Mice

Hexane Extracts of Calophyllum brasiliense Inhibit the Development of Gastric Preneoplasia in Helicobacter felis Infected INS-Gas Mice

Chromone as a Privileged Scaffold in Drug Discovery: Recent Advances

Suzuki–Miyaura Cross‐Coupling Reactions of Tetrahydroxanthones and 4‐Chromanone Lactones to Heteromeric Biaryls

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