Discovery of Novel Pyridazine-Tethered Sulfonamides as Carbonic Anhydrase II Inhibitors for the Management of Glaucoma

Journal of Medicinal Chemistry, Год журнала: 2024, Номер 67(2), С. 1611 - 1623

Опубликована: Янв. 11, 2024

As a progressive neuropathic condition, glaucoma can cause lifelong blindness if left untreated. Novel phenylpyridazine-tethered sulfonamides were designed as selective inhibitors for carbonic anhydrase (CA) isoform II to find effective therapeutic agents glaucoma. Subsequently, the target synthesized and assessed their inhibitory action against cytosolic CA I II. Interestingly, molecules poorly inhibited while exhibiting low subnanomolar potency Compound

Язык: Английский

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Development of new thieno[2,3-d]pyrimidines as dual EGFR and STAT3 inhibitors endowed with anticancer and pro-apoptotic activities

Bioorganic Chemistry, Год журнала: 2024, Номер 143, С. 107101 - 107101

Опубликована: Янв. 4, 2024

Язык: Английский

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Discovery and Mechanistic Studies of Dual-Target Hits for Carbonic Anhydrase IX and VEGFR-2 as Potential Agents for Solid Tumors: X-ray, In Vitro, In Vivo, and In Silico Investigations of Coumarin-Based Thiazoles

Journal of Medicinal Chemistry, Год журнала: 2024, Номер 67(9), С. 7406 - 7430

Опубликована: Апрель 20, 2024

A dual-targeting approach is predicted to yield better cancer therapy outcomes. Consequently, a series of coumarin-based thiazoles (5a–h, 6, and 7a–e) were designed constructed as potential carbonic anhydrase (CA) VEGFR-2 suppressors. The inhibitory actions the target compounds assessed against CA isoforms IX VEGFR-2. assay results showed that 5a, 5d, 5e can effectively inhibit both targets. cytotoxic effects tested on pancreatic, breast, prostate cells (PANC1, MCF7, PC3). Further mechanistic investigation disclosed ability interrupt PANC1 cell progression in S stage by triggering apoptotic cascade, seen increased levels caspases 3, 9, BAX, alongside Bcl-2 decline. Moreover, vivo efficacy compound an antitumor agent was evaluated. Also, molecular docking dynamics displayed distinctive interactions between binding pockets.

Язык: Английский

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A new framework for novel analogues of pazopanib as potent and selective human carbonic anhydrase inhibitors: Design, repurposing rational, synthesis, crystallographic, in vivo and in vitro biological assessments

European Journal of Medicinal Chemistry, Год журнала: 2024, Номер 274, С. 116527 - 116527

Опубликована: Май 24, 2024

Язык: Английский

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Novel imidazo[2,1-b]thiazoles and imidazo[1,2-a]pyridines tethered with indolinone motif as VEGFR-2 inhibitors and apoptotic inducers: Design, synthesis and biological evaluations

Bioorganic Chemistry, Год журнала: 2024, Номер 151, С. 107644 - 107644

Опубликована: Июль 15, 2024

Язык: Английский

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Novel sulfonamide-tethered Schiff bases as anti-proliferative agents with VEGFR-2 inhibitory activity: Synthesis, biological assessment, and molecular dynamic simulations

Journal of Molecular Structure, Год журнала: 2024, Номер 1309, С. 138148 - 138148

Опубликована: Март 26, 2024

Язык: Английский

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Unveiling the potential of isatin-grafted phenyl-1,2,3-triazole derivatives as dual VEGFR-2/STAT-3 inhibitors: Design, synthesis and biological assessments

Bioorganic Chemistry, Год журнала: 2024, Номер 151, С. 107626 - 107626

Опубликована: Июль 10, 2024

Язык: Английский

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Synthesis and biological evaluation of 1-phenyl-tetrahydro-β-carboline-based first dual PRMT5/EGFR inhibitors as potential anticancer agents

European Journal of Medicinal Chemistry, Год журнала: 2024, Номер 269, С. 116341 - 116341

Опубликована: Март 18, 2024

Язык: Английский

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Discovery of new sulfonamide-tethered 2-aryl-4-anilinoquinazolines as the first-in-class dual carbonic anhydrase and EGFR inhibitors

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 279, С. 135010 - 135010

Опубликована: Авг. 26, 2024

Язык: Английский

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Design, synthesis, molecular docking and dynamic studies of novel thienopyrimidine analogs linked to 1,2,3-triazole-bearing acetamide derivatives as anti-oxidant agents

Journal of Molecular Structure, Год журнала: 2024, Номер 1307, С. 137883 - 137883

Опубликована: Фев. 29, 2024

Язык: Английский

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