2‐Indolinone: An Anticancer Scaffold, Overview of the Studies and Approaches (2017–2024)

ChemistrySelect, Год журнала: 2025, Номер 10(5)

Опубликована: Фев. 1, 2025

Abstract 2‐Indolinone is a versatile scaffold that has been the central moiety in structure of various drugs. Since introduction sunitinib malate, 2‐indolinones have principal pharmacophoric building block many drug discovery studies, especially last few years. Compounds bearing 2‐indolinone ring system shown therapeutic effects, including but not limited to, antidiabetic, antioxidant, anti‐inflammatory, anti‐HIV, antimicrobial, antipsychotic, antiparkinson, and anticancer activities. Considering cancer among major global causes death, antiproliferative activities these compounds goal numerous studies. The present review presents an overview approaches advances made during eight years (2017–2024) regarding development derivatives within field discovery. derivates gathered herein are classified according to target developed compounds, notable structure‐activity relationships as well significant molecular docking interactions with enzymes highlighted each instance. Accordingly, special attention paid reporting superior enzymatic inhibitory effects emerged lead respective study.

Язык: Английский

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Novel 5,6-dichlorobenzimidazole derivatives as dual BRAFWT and BRAFV600E inhibitors: design, synthesis, anti-cancer activity and molecular dynamics simulations

BMC Chemistry, Год журнала: 2025, Номер 19(1)

Опубликована: Фев. 21, 2025

Язык: Английский

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Design and synthesis of novel pyrimidine-pyrazole hybrids with dual anticancer and anti-inflammatory effects targeting BRAFV600E and JNK

Molecular Diversity, Год журнала: 2025, Номер unknown

Опубликована: Фев. 22, 2025

Abstract Two new series of pyrimidinyl ethyl pyrazoles derivatives 13a–f and 14a–f were designed synthesized to possess both anticancer effect by inhibiting BRAFV600E anti-inflammatory JNK isoforms. The structure the compounds was generated from hybridization two main moieties. moiety reported inhibitors, pyrazole isoforms inhibitors. final tested on BRAFV600E, JNK1, JNK2, JNK3 measure their kinases inhibitory effect. Compound 14c showed highest activity with IC 50 = 0.51 μM, 0.53 1.02 0.009 μM JNK3,and respectively. All over four cancer cell lines related target enzymes. 14d most potent all 0.87 0.91, 0.42 0.63 MOLT-4, K-562, SK-MEL-28, A375 lines, ability inhibit MEK1/2 ERK1/2 phosphorylation performed using western blot. cycle analysis compound line revealed that arrested growth at G0-G1 phase. remarkably decreased migration compared control group in traditional test. Compounds significant nitric oxide release PGE2 production raw 264.7 macrophages. 13d 1 4d exhibited high iNOS COX-2 COX-1. Finally, TNF-alpha IL-6 determined. Graphical abstract synthesized. able BRAFV600E. play a key role inflammatory disorders. Final for activities.

Язык: Английский

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A Comprehensive Review of RAF Kinase: Advances in Inhibition Strategies for Drug Development

Journal of Molecular Structure, Год журнала: 2025, Номер unknown, С. 142206 - 142206

Опубликована: Март 1, 2025

Язык: Английский

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Development of indole hybrids for potential lung cancer treatment - part II

Future Medicinal Chemistry, Год журнала: 2025, Номер unknown, С. 1 - 17

Опубликована: Март 30, 2025

Lung cancer has become the most prevalent for past three decades, and 5-years survival rate of lung is only ~20% nowadays. Chemotherapy mainstay therapy, especially non-small cell cancer. However, drug resistance represents a principal cause therapeutic failure in leading to insensitivity, tumor recurrence, disease progression. Indole hybrids have potential conquer resistance, enhance efficacy, reduce adverse events, improve pharmacokinetic properties due their capacity inhibit multiple targets simultaneously. Moreover, indole osimertinib, mobocertinib, cediranib, vizimpro are currently applied clinics demonstrating that valuable scaffolds treatment eradication This review provides comprehensive overview evolving landscape with vitro vivo efficacy against cancer, structure–activity relationships as well mechanisms action also discussed, covering articles published from 2021 onward.

Язык: Английский

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Investigating novel tubulin polymerization inhibitors: design, synthesis, LC/MS cellular permeability, in silico studies, and in vitro assessment

Medicinal Chemistry Research, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 11, 2024

Язык: Английский

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