Diphenylaminothiophen-derived fluorescent ligands targeting mitochondrial DNA G-quadruplexes potentially for triple-negative breast cancer therapy

International Journal of Biological Macromolecules, Год журнала: 2025, Номер 302, С. 140556 - 140556

Опубликована: Янв. 31, 2025

Язык: Английский

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Discovery of a mitochondrial G-quadruplex targeted fluorescent ligand via a slight variation on the near-infrared heptamethine cyanine scaffold

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 269, С. 132230 - 132230

Опубликована: Май 8, 2024

Язык: Английский

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Targeting the G-quadruplex as a novel strategy for developing antibiotics against hypervirulent drug-resistant Staphylococcus aureus

Journal of Biomedical Science, Год журнала: 2025, Номер 32(1)

Опубликована: Фев. 5, 2025

Abstract Background The rapid emergence of multiple drug-resistant (MDR) bacterial pathogens and the lack a novel antibiotic pipeline pose serious threat to global healthcare. limited number established targets further restricts identification antibiotics treat life-threatening MDR infections caused by Staphylococcus aureus strains. Therefore, for developing are urgently required. In this study, we hypothesized that G-quadruplex (G4)-binding ligands can be used as their binding possibly downregulate/block expression vital genes. Methods To test this, first screened properties representative G4-binding against hypervirulent S. USA300 determined in vitro vivo antibacterial activity; proposed mechanism action applying various microbiological, infection, microscopic, biophysicochemical techniques. Results Herein, among ligands, N-methyl mesoporphyrin IX (NMM) showed highest activity USA300. NMM exhibited minimum inhibitory concentration (MIC) 5 μM USA300, impacting cell division wall repressing expressions genes ( dcw ) gene cluster. Genome-wide bioinformatics analysis G4 motifs mapping on genome, identified presence G4-motif promoter mraZ , conserved master regulator cluster regulating coordinated synthesis. Physicochemical assessments using UV–visible, circular dichroism, nuclear magnetic resonance spectroscopy confirmed present formed an intramolecular parallel structure, interacting with NMM. reporter followed coupled transcription/translation (IVT) assays role target impose extreme both gram-positive -negative bacteria. In-cell validation RAW264.7 cells Galleria mellonella ; respectively, demonstrated superior compared well-established antibiotics, no observed cytotoxicity. Conclusions summary, current study broad-spectrum potent agent elucidated its plausible primarily targeting

Язык: Английский

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Mitochondrial DNA-targeted triphenylamine-thiophene (TPATP)-derived ligands boost type-I/II photodynamic therapy for triple-negative breast cancer

European Journal of Medicinal Chemistry, Год журнала: 2025, Номер 289, С. 117489 - 117489

Опубликована: Март 7, 2025

Язык: Английский

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G-quadruplex in cancer energy metabolism: A potential therapeutic target

Biochimica et Biophysica Acta (BBA) - General Subjects, Год журнала: 2025, Номер unknown, С. 130810 - 130810

Опубликована: Апрель 1, 2025

Язык: Английский

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Design and synthesis of novel mitochondria-targeted ergosterol peroxide derivatives as potential anti-cancer agents

Bioorganic Chemistry, Год журнала: 2024, Номер 153, С. 107862 - 107862

Опубликована: Окт. 1, 2024

Язык: Английский

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A highly emissive near infrared thiophene-benzoindolium ligand binding to mitochondrial G-quadruplexes triggers triple-negative breast cancer cell death

Sensors and Actuators B Chemical, Год журнала: 2024, Номер 418, С. 136350 - 136350

Опубликована: Июль 23, 2024

Язык: Английский

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A NRAS mRNA G-quadruplex structure-targeting small-molecule ligand reactivating DNA damage response in human cancer cells for combination therapy with clinical PI3K inhibitors

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 279, С. 135308 - 135308

Опубликована: Сен. 6, 2024

Язык: Английский

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Insight into Stabilization of G‐Quadruplex in c‐MYC Region with Phenanthroimidazoisoindol‐Acrylates and their Binding Behaviour towards Human Serum Albumin

ChemMedChem, Год журнала: 2024, Номер unknown

Опубликована: Дек. 16, 2024

The interaction of G-quadruplex (non-canonical DNA) with suitable compounds for their stabilization at the promoter region oncogenes has become a potential anticancer approach. We have studied phenanthroimidazoisoindol-acrylates derivatives c-MYC G-quadruplex. A series 20 were evaluated activity against human cancer cell lines, where 3 fa, ha, and ae shown broad-spectrum activities most lines inactive towards normal lines. Various spectroscopic techniques been used to study these compounds. studies reveal strong binding all three significant selectivity over dsDNA, constant order 10

Язык: Английский

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A correlation of polymorphic G-quadruplex formation in vitro and in the lysosomes of live cancer cells

International Journal of Biological Macromolecules, Год журнала: 2024, Номер unknown, С. 138899 - 138899

Опубликована: Дек. 1, 2024

Язык: Английский

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