Bioactivities and Action Mechanisms of Ellipticine Derivatives Reported Prior to 2023

Chemistry & Biodiversity, Год журнала: 2024, Номер 21(5)

Опубликована: Март 4, 2024

Abstract Currently, natural products are one of the priceless options for finding novel chemical pharmaceutical entities. Ellipticine is a naturally occurring alkaloid isolated from leaves Ochrosia elliptica Labill . and its derivatives characterized by multiple biological activities. The purpose this review was to provide critical systematic assessment ellipticine as bioactive molecules over last 60 years. Publications focused mainly on total synthesis alkaloids type without any evaluation bioactivity have been excluded. We reviewed papers dealing with synthesis, mechanism action derivatives. It found that showed cytotoxicity, antimicrobial ability, anti‐inflammatory activity, among which cytotoxicity toward cancer cell lines most investigated aspect. inhibition DNA topoisomerase II relevant cytotoxicity. PI3K/AKT pathway, p53 MAPK pathway were also closely related antiproliferative ability these compounds. In addition, structure‐activity relationship deduced, future prospects outlined. confident findings will lay scientific foundation ellipticine‐based drug development, especially anticancer agents.

Язык: Английский

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Enhanced inhibitory activity of compounds containing purine scaffolds compared to protein kinase CK2α considering crystalline water

RSC Medicinal Chemistry, Год журнала: 2024, Номер 15(4), С. 1274 - 1282

Опубликована: Янв. 1, 2024

The design of the complex structure CK2α and inhibitor, leaving crystalline water molecules in structure, significantly increased inhibitory activity.

Язык: Английский

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Development and therapeutic perspectives of CXCR4 antagonists for disease therapy

European Journal of Medicinal Chemistry, Год журнала: 2024, Номер 275, С. 116594 - 116594

Опубликована: Июнь 11, 2024

Язык: Английский

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Discovery of a CK2α′-Biased ATP-Competitive Inhibitor from a High-Throughput Screen of an Allosteric-Inhibitor-Like Compound Library

ACS Chemical Neuroscience, Год журнала: 2024, Номер 15(15), С. 2703 - 2718

Опубликована: Июнь 22, 2024

Protein kinase CK2 is a holoenzyme composed of two regulatory subunits (CK2β) and catalytic (CK2α CK2α′). controls several cellular processes, including proliferation, inflammation, cell death. However, CK2α CK2α′ possess different expression patterns substrates therefore impact each these processes differently. Elevated participates in the development cancer, while increased has been associated with neurodegeneration, especially Huntington's disease (HD). HD fatal for which no effective therapies are available. Genetic deletion mouse models ameliorated neurodegeneration. Therefore, pharmacological inhibition presents promising therapeutic strategy treating HD. current inhibitors unable to discriminate between due their high structural homology, targeted ATP-binding site. Using computational analyses, we found potential type IV ("D" pocket) allosteric site that contained residues was distal from pocket featured both kinases. We decided look modulators might interact biased fashion on CK2α′. screened commercial library containing ∼29,000 allosteric-kinase-inhibitor-like compounds using activity-dependent ADP-Glo Kinase assay. Obtained hits were counter-screened against assay, revealing CK2α′-biased compounds. These serve as basis further medicinal chemistry optimization treatment

Язык: Английский

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Identification of potential natural product derivatives as CK2 inhibitors based on GA-MLR QSAR modeling, synthesis and biological evaluation

Medicinal Chemistry Research, Год журнала: 2024, Номер 33(9), С. 1611 - 1624

Опубликована: Июль 10, 2024

Язык: Английский

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