Synthesis and Antitumor Activity of 2,3-Diphenyl-2H-indazole Derivatives as Potent Antitubulin Agents

被引：1

作者：

Matadamas-Martinez, Felix ^{[1
]}

Yepez-Mulia, Lilian ^{[2
]}

Perez-Koldenkova, Vadim ^{[3
]}

Cortes-Benitez, Francisco ^{[1
]}

Leyte-Lugo, Martha ^{[4
]}

Palacios-Espinosa, Juan Francisco ^{[1
]}

Rodriguez-Villar, Karen ^{[1
]}

Soria-Arteche, Olivia ^{[1
]}

Perez-Villanueva, Jaime ^{[1
]}

机构：

[1] Univ Autonoma Metropolitana Xochimilco UAM Mexico, Div Ciencias Biol Salud, Dept Sistemas Biol, Mexico City 04960, DF, Mexico

[2] Pediat Ctr Med Nacl Siglo XXI, Inst Mexicano Seguro Social, Unidad Med Alta Especialidad Hosp Pediat, Unidad Invest Med Enfermedades Infecc & Parasitar, Mexico City 06720, DF, Mexico

[3] Nacl Siglo XXI, Ctr Med Nacl Siglo XXI, Inst Mexicano Seguro Social, Lab Nacl Microscopia Avanzada Ctr Med, Mexico City 06720, DF, Mexico

[4] Univ Autonoma Metropolitana Xochimilco UAM X, Div Ciencias Biol & Salud, Catedrat CONACYT Comisionado, Dept Sistemas Biol, Mexico City 04960, DF, Mexico

来源：

CHEMISTRYSELECT | 2022年 / 7卷 / 27期

关键词：

Cancer; Combretastatin A-4; Cytotoxicity; Hybrid compounds; Indazole; MITOTIC CATASTROPHE; CYTOTOXIC ACTIVITY; CELL-DEATH; PACLITAXEL; APOPTOSIS; BINDING; MITOSIS; CYCLE;

D O I：

10.1002/slct.202202056

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

We contribute with the design and synthesis of novel 2,3-diphenyl-2H-indazole hybrids series (1-14). Compounds 4 and 6 had the highest antiproliferative activity against the cancer cell lines, HeLa, SK-LU-1, K-562, PC-3, SW620 and MCF-7 (CC50 values from 3 to 5.4 mu M). Their activity was also evaluated against a normal human cell line, showing their higher Selectivity Index against the cancer cell lines than the reference drug CA-4. The inhibition of tubulin assembly by compounds 4 and 6 was determined using in vitro tubulin polymerization assay and Western Blotting. The induction of mitotic catastrophe was observed with immunofluorescence assays. Besides, it was demonstrated by flow cytometry that compounds 4 and 6 arrest HeLa cell cycle at G2/M and promote apoptotic cell death. The mitotic arrest was also associated with elevated levels of cyclin B1 protein. We have identified two hybrids that behave as microtubule-destabilizing agents on different cancer cell lines.

引用

页数：10

共 34 条

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