Discovery of novel pyrrolo[2,3-b]pyridine derivatives bearing 4-oxoquinoline moiety as potential antitumor inhibitor

Huimin Liu; Yongli Duan; Hehua Xiong; Jianqing Zhang; Shunmin Huang; Ting Chen; Pengwu Zheng; Qidong Tang

doi:10.1016/j.bmcl.2019.126848

Discovery of novel pyrrolo[2,3-b]pyridine derivatives bearing 4-oxoquinoline moiety as potential antitumor inhibitor

Bioorg Med Chem Lett. 2020 Jan 15;30(2):126848. doi: 10.1016/j.bmcl.2019.126848. Epub 2019 Dec 2.

Authors

Huimin Liu¹, Yongli Duan², Hehua Xiong³, Jianqing Zhang³, Shunmin Huang³, Ting Chen³, Pengwu Zheng⁴, Qidong Tang⁵

Affiliations

¹ School of Perfume and Aroma Technology, Shanghai Institute of Technology; Engineering Research Center of Perfume & Aroma and Cosmetics of Ministry of Education, Shanghai 201418, PR China.
² Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, PR China; School of Optoelectronic Science and Engineering, University of Electronic Science and Technology of China (UESTC), Chengdu 610054, PR China.
³ Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, PR China.
⁴ Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, PR China. Electronic address: zhengpw@126.com.
⁵ Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, PR China. Electronic address: tangqidongcn@126.com.

PMID: 31836443
DOI: 10.1016/j.bmcl.2019.126848

Abstract

A series of pyrrolo[2,3-b]pyridine derivatives bearing 4-oxoquinoline moiety were designed, synthesized and evaluated for the anti-proliferative on three cancer cell lines (A549, HepG2 and MCF-7) in vitro. Most of the compounds showed moderate to high potency. Some excellent compounds were tested for the inhibitory activity of c-Met kinase. Compound 34 (c-Met IC₅₀ = 17 nM) was investigated the selectivity against Flt-3, c-Kit, VEGFR-2, ALK, PDGFR-β and RON. Structure-activity relationship studies indicated that hydrogen, fluorine atom, and mono-electron-withdrawing groups (mono-EWGs, such as R² = F) on R, R¹ and R², respectively, were beneficial for the anti-proliferative activities of the target compounds. Besides, we have took further study on the combined mode between compound 34 and c-Met kinase through molecular docking.

Keywords: 4-Oxoquinoline; Anti-proliferative activity; Pyrrolo[2,3-b]pyridine derivatives; Synthesis; c-Met.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

4-Quinolones / chemical synthesis*
4-Quinolones / chemistry
Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use*
Humans
Molecular Structure
Pyridines / chemical synthesis*
Pyridines / chemistry
Structure-Activity Relationship

Substances

4-Quinolones
Antineoplastic Agents
Pyridines