Discovery of novel conjugates of quinoline and thiazolidinone urea as potential anti-colorectal cancer agent

Li Xionga Department of Bioengineering, Zhuhai Campus of Zunyi Medical University, Zhuhai, China;b Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, Zunyi Medical University, Zunyi, ChinaView further author information

Huan Hea Department of Bioengineering, Zhuhai Campus of Zunyi Medical University, Zhuhai, ChinaView further author information

Mengmeng Fana Department of Bioengineering, Zhuhai Campus of Zunyi Medical University, Zhuhai, China;b Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, Zunyi Medical University, Zunyi, ChinaView further author information

Liping Hua Department of Bioengineering, Zhuhai Campus of Zunyi Medical University, Zhuhai, China;b Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, Zunyi Medical University, Zunyi, ChinaView further author information

Fei Wanga Department of Bioengineering, Zhuhai Campus of Zunyi Medical University, Zhuhai, China;b Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, Zunyi Medical University, Zunyi, ChinaView further author information

Xiaomeng Songa Department of Bioengineering, Zhuhai Campus of Zunyi Medical University, Zhuhai, China;b Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, Zunyi Medical University, Zunyi, ChinaView further author information

Shengmin Shia Department of Bioengineering, Zhuhai Campus of Zunyi Medical University, Zhuhai, China;b Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, Zunyi Medical University, Zunyi, ChinaView further author information

Baohui Qia Department of Bioengineering, Zhuhai Campus of Zunyi Medical University, Zhuhai, China;b Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, Zunyi Medical University, Zunyi, ChinaCorrespondence[email protected]
View further author information

show all

Abstract

Based on the obtained SARs, further structural optimisation of compound BC2021-104511-15i was conducted in this investigation, and totally ten novel quinoline derivates were designed, synthesised and optimised for biological activity. Among them, compound 10a displayed significant in vitro anticancer activity against COLO 205 cells with an IC₅₀ value of 0.11 μM which was over 90-fold more potent than that of Regorafenib (IC₅₀>10.0 μM) and Fruquintinib (IC₅₀>10.0 μM). Furthermore, compound 10a exhibited over 90-fold selectivity towards COLO 205 relative to human normal colorectal mucosa epithelial cell FHC cells. Flow cytometry study demonstrated that compound 10a could induce apoptosis in COLO 205 cells, however, it could not induce cell cycle arrest in COLO 205 cells. The results of preliminary kinase profile study showed that compound 10a was a potential HGFR and MST1R dual inhibitor, with IC₅₀ values of 0.11 μM and 0.045 μM, respectively.

Keywords:

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by Science and Technology Projects of Guizhou Province (Qian Ke He Foundation-ZK[2021]key project 015).

Discovery of novel conjugates of quinoline and thiazolidinone urea as potential anti-colorectal cancer agent

Information for

Open access

Opportunities

Help and information

Discovery of novel conjugates of quinoline and thiazolidinone urea as potential anti-colorectal cancer agent

Abstract

Disclosure statement

Additional information

Funding

Related research

To cite this article:

Download citation

Information for

Open access

Opportunities

Help and information

Keep up to date

Your download is now in progress and you may close this window

Login or register to access this feature