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Discovery of Simple Diacylhydrazine-Functionalized Cinnamic Acid Derivatives as Potential Microtubule Stabilizers

To develop novel microtubule-binding agents for cancer therapy, an array of N-cinnamoyl-N’-(substituted)acryloyl hydrazide derivatives were facilely synthesized through a two-step process. Initially, the antiproliferative activity of these title compounds was explored against A549, 98 PC-3 and HepG2...

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Detalles Bibliográficos
Autores principales: Zhou, Xiang, Fu, Yi-Hong, Zou, Ya-Yu, Meng, Jiao, Ou-Yang, Gui-Ping, Ge, Qiang-Sheng, Wang, Zhen-Chao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604255/
https://www.ncbi.nlm.nih.gov/pubmed/36293224
http://dx.doi.org/10.3390/ijms232012365
Descripción
Sumario:To develop novel microtubule-binding agents for cancer therapy, an array of N-cinnamoyl-N’-(substituted)acryloyl hydrazide derivatives were facilely synthesized through a two-step process. Initially, the antiproliferative activity of these title compounds was explored against A549, 98 PC-3 and HepG2 cancer cell lines. Notably, compound I(23) exhibited the best antiproliferative activity against three cancer lines with IC(50) values ranging from 3.36 to 5.99 μM and concurrently afforded a lower cytotoxicity towards the NRK-52E cells. Anticancer mechanism investigations suggested that the highly bioactive compound I(23) could potentially promote the protofilament assembly of tubulin, thus eventually leading to the stagnation of the G2/M phase cell cycle of HepG2 cells. Moreover, compound I(23) also disrupted cancer cell migration and significantly induced HepG2 cells apoptosis in a dosage-dependent manner. Additionally, the in silico analysis indicated that compound I(23) exhibited an acceptable pharmacokinetic profile. Overall, these easily prepared N-cinnamoyl-N’-(substituted)acryloyl hydrazide derivatives could serve as potential microtubule-interacting agents, probably as novel microtubule-stabilizers.