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Synthesis and Evaluation of Novel 2-Pyrrolidone-Fused (2-Oxoindolin-3-ylidene)methylpyrrole Derivatives as Potential Multi-Target Tyrosine Kinase Receptor Inhibitors

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Název: Synthesis and Evaluation of Novel 2-Pyrrolidone-Fused (2-Oxoindolin-3-ylidene)methylpyrrole Derivatives as Potential Multi-Target Tyrosine Kinase Receptor Inhibitors
Autoři: Ting-Hsuan Yang, Chun-I Lee, Wen-Hsin Huang, An-Rong Lee
Zdroj: Molecules ; Volume 22 ; Issue 6 ; Pages: 913
Informace o vydavateli: Multidisciplinary Digital Publishing Institute
Rok vydání: 2017
Sbírka: MDPI Open Access Publishing
Témata: multi-target kinase inhibitor, VEGFR-2 inhibitor, PDGFRβ inhibitor angiogenesis, (2-oxoindolin-3-ylidene)methylpyrrole
Geografické téma: agris
Popis: Signaling pathways of VEGFs and PDGFs are crucial in tumor angiogenesis, which is essential in solid tumor progression and metastasis. This study reports our strategy for designing and synthesizing a series of novel 2-pyrrolidone-fused (2-oxoindolin-3-ylidene)methylpyrrole derivatives as potential multi-target tyrosine kinase receptor inhibitors. The target compounds were obtained by condensation of 5-substituted oxindoles with N-substituted 2-pyrrolidone aldehyde 7 in satisfactory yields. Of these, 11 and 12 had the highest potency and, compared to sunitinib, showed: (1) significant increase in anti-proliferation of various cancer cells with a favorable selective index (SI); (2) higher inhibitory potency against both VEGFR-2 and PDGFRβ. The molecular modeling results showed that, in terms of VEGFR-2 binding, the synthesized products had a similar binding mode to sunitinib but with tighter interaction.
Druh dokumentu: text
Popis souboru: application/pdf
Jazyk: English
Relation: Medicinal Chemistry; https://dx.doi.org/10.3390/molecules22060913
DOI: 10.3390/molecules22060913
Dostupnost: https://doi.org/10.3390/molecules22060913
Rights: https://creativecommons.org/licenses/by/4.0/
Přístupové číslo: edsbas.76DF31D5
Databáze: BASE
Popis
Abstrakt:Signaling pathways of VEGFs and PDGFs are crucial in tumor angiogenesis, which is essential in solid tumor progression and metastasis. This study reports our strategy for designing and synthesizing a series of novel 2-pyrrolidone-fused (2-oxoindolin-3-ylidene)methylpyrrole derivatives as potential multi-target tyrosine kinase receptor inhibitors. The target compounds were obtained by condensation of 5-substituted oxindoles with N-substituted 2-pyrrolidone aldehyde 7 in satisfactory yields. Of these, 11 and 12 had the highest potency and, compared to sunitinib, showed: (1) significant increase in anti-proliferation of various cancer cells with a favorable selective index (SI); (2) higher inhibitory potency against both VEGFR-2 and PDGFRβ. The molecular modeling results showed that, in terms of VEGFR-2 binding, the synthesized products had a similar binding mode to sunitinib but with tighter interaction.
DOI:10.3390/molecules22060913