Design, synthesis, and biological evaluation of diarylpyrazole derivatives as antitumor agents targeting microtubules

Jing Chang; Chao Wang; Shanbo Yang; Lingyu Shi; Yujing Zhang; Wenjing Liu; Jingsen Meng; Jun Zeng; Renshuai Zhang; Ning Liu; Dongming Xing

Arabian Journal of Chemistry (Nov 2022)

Design, synthesis, and biological evaluation of diarylpyrazole derivatives as antitumor agents targeting microtubules

Jing Chang,
Chao Wang,
Shanbo Yang,
Lingyu Shi,
Yujing Zhang,
Wenjing Liu,
Jingsen Meng,
Jun Zeng,
Renshuai Zhang,
Ning Liu,
Dongming Xing

Affiliations

Jing Chang: School of Basic Medicine, Qingdao University, Qingdao 266071, Shandong, China; The Affiliated Hospital of Qingdao University, Cancer Institute, Qingdao University, Qingdao 266071, Shandong, China
Chao Wang: The Affiliated Hospital of Qingdao University, Cancer Institute, Qingdao University, Qingdao 266071, Shandong, China; Corresponding authors at: The Affiliated Hospital of Qingdao University, Cancer Institute, Qingdao University, Qingdao 266071, Shandong, China (D. Xing).
Shanbo Yang: School of Basic Medicine, Qingdao University, Qingdao 266071, Shandong, China; The Affiliated Hospital of Qingdao University, Cancer Institute, Qingdao University, Qingdao 266071, Shandong, China
Lingyu Shi: School of Basic Medicine, Qingdao University, Qingdao 266071, Shandong, China; The Affiliated Hospital of Qingdao University, Cancer Institute, Qingdao University, Qingdao 266071, Shandong, China
Yujing Zhang: The Affiliated Cardiovascular Hospital of Qingdao University, Qingdao University, Qingdao 266071, Shandong, China
Wenjing Liu: School of Basic Medicine, Qingdao University, Qingdao 266071, Shandong, China; The Affiliated Hospital of Qingdao University, Cancer Institute, Qingdao University, Qingdao 266071, Shandong, China
Jingsen Meng: School of Basic Medicine, Qingdao University, Qingdao 266071, Shandong, China; The Affiliated Hospital of Qingdao University, Cancer Institute, Qingdao University, Qingdao 266071, Shandong, China
Jun Zeng: School of Basic Medicine, Qingdao University, Qingdao 266071, Shandong, China; The Affiliated Hospital of Qingdao University, Cancer Institute, Qingdao University, Qingdao 266071, Shandong, China
Renshuai Zhang: The Affiliated Hospital of Qingdao University, Cancer Institute, Qingdao University, Qingdao 266071, Shandong, China
Ning Liu: The Affiliated Hospital of Qingdao University, Cancer Institute, Qingdao University, Qingdao 266071, Shandong, China; Corresponding authors at: The Affiliated Hospital of Qingdao University, Cancer Institute, Qingdao University, Qingdao 266071, Shandong, China (D. Xing).
Dongming Xing: The Affiliated Hospital of Qingdao University, Cancer Institute, Qingdao University, Qingdao 266071, Shandong, China; School of Life Sciences, Tsinghua University, Beijing 100084, China; Corresponding authors at: The Affiliated Hospital of Qingdao University, Cancer Institute, Qingdao University, Qingdao 266071, Shandong, China (D. Xing).

Journal volume & issue: Vol. 15, no. 11
p. 104253

Abstract

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A new series of novel diarylpyrazole derivatives as microtubule destabilizers were synthesized and evaluated for the anti-proliferative activities. Anti-proliferative assays were performed on the human cervix adenocarcinoma cell line (HeLa) and human gastric adenocarcinoma cell line (SGC-7901), and the compound 9s containing indole ring showed great anti-proliferative activity against HeLa cells with IC50 value of 1.9 ± 0.11 μM. Further biological studies showed that 9s was able to inhibit tubulin polymerization, disrupt the cytoskeleton, block the cell cycle in the G2/M phase, and induce cell apoptosis in a concentration-dependent manner. In addition, the results of molecular docking studies showed that compound 9s could bind tightly to the colchicine binding site of tubulin through hydrogen bonding interaction. These preliminary results recommend that compound 9s is likely to be a microtubule destabilizer that deserves further investigation.

Published in Arabian Journal of Chemistry

ISSN: 1878-5352 (Print)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Chemistry
Website: http://www.journals.elsevier.com/arabian-journal-of-chemistry/

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