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Review
. 2023 Mar 1:11:1096666.
doi: 10.3389/fchem.2023.1096666. eCollection 2023.

Research progress on antitumor activity of XRP44X and analogues as microtubule targeting agents

Chao Wang  1 , Lingyu Shi  1   2 , Shanbo Yang  1   2 , Jing Chang  1   2 , Wenjing Liu  1   2 , Jun Zeng  1   2 , Jingsen Meng  1   2 , Renshuai Zhang  1 , Dongming Xing  1   3
Affiliations
Review

Research progress on antitumor activity of XRP44X and analogues as microtubule targeting agents

Chao Wang et al. Front Chem. .

Abstract

Cancer threatens human health and life. Therefore, it is particularly important to develop safe and effective antitumor drugs. Microtubules, the main component of cytoskeleton, play an important role in maintaining cell morphology, mitosis, and signal transduction, which are one of important targets of antitumor drug research and development. Colchicine binding site inhibitors have dual effects of inhibiting proliferation and destroying blood vessels. In recent years, a series of inhibitors targeting this target have been studied and some progress has been made. XRP44X has a novel structure and overcomes some disadvantages of traditional inhibitors. It is also a multifunctional molecule that regulates not only the function of tubulin but also a variety of biological pathways. Therefore, the structure, synthesis, structure-activity relationship, and biological activity of XRP44X analogues reported in recent years were summarized in this paper, to provide a useful reference for the rational design of efficient colchicine binding site inhibitors.

Keywords: SAR; XRP44X; antitumor activity; colchicine binding site inhibitors; structural modification.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Chemical structures of some colchicine binding site inhibitors.
FIGURE 2
FIGURE 2
The binding mode of XRP44X against tubulin.
FIGURE 3
FIGURE 3
The mechanism of action of XRP44X.
FIGURE 4
FIGURE 4
Synthetic strategy for compound 16 and SAR.
FIGURE 5
FIGURE 5
Synthetic strategy for compound 20 and SAR.
FIGURE 6
FIGURE 6
Synthetic strategy for compounds 25, 26, and SAR.
FIGURE 7
FIGURE 7
Synthetic strategy for compound 31 and SAR.
FIGURE 8
FIGURE 8
Synthetic strategy for compound 35, 36, and 41.
FIGURE 9
FIGURE 9
SAR and active molecules of aryloxazole analogues.
FIGURE 10
FIGURE 10
Structure of six-membered heterocyclic hybrid analogues.
FIGURE 11
FIGURE 11
Structure of aryl piperidine analogues.
FIGURE 12
FIGURE 12
Structure and activity of homopiperazine analogues.
FIGURE 13
FIGURE 13
New anti-influenza agents targeting virus nucleoprotein.
See this image and copyright information in PMC

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