PMID- 32685812
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2470-1343 (Electronic)
IS  - 2470-1343 (Linking)
VI  - 5
IP  - 27
DP  - 2020 Jul 14
TI  - Discovery of Triazolo-pyridazine/-pyrimidine Derivatives Bearing Aromatic 
      (Heterocycle)-Coupled Azole Units as Class II c-Met Inhibitors.
PG  - 16482-16490
LID - 10.1021/acsomega.0c00838 [doi]
AB  - Two series of novel triazolo-pyridazine/-pyrimidine derivatives were designed, 
      synthesized, and evaluated for their inhibitory activity against c-Met kinase, as 
      well as three c-Met overexpressed cancer cell lines (A549, MCF-7, and HeLa) and 
      one normal human hepatocytes cell line LO2 in vitro. The pharmacological data 
      indicated that most of the tested compounds showed moderate cytotoxicity, and the 
      most promising compound 12e exhibited significant cytotoxicity against A549, 
      MCF-7, and HeLa cell lines with IC(50) values of 1.06 +/- 0.16, 1.23 +/- 0.18, and 
      2.73 +/- 0.33 muM, respectively. Moreover, the inhibitory activity of compound 12e 
      against c-Met kinase (IC(50) = 0.090 muM) was equal to that of Foretinib (IC(50) = 
      0.019 muM). The result of the acridine orange (AO) single staining test 
      demonstrated that compound 12e could remarkably induce apoptosis of A549 cells. 
      The results of apoptosis and cycle distribution of cells showed that compound 12e 
      could induce late apoptosis of A549 cells and stimulate A549 cells arresting in 
      the G0/G1 phase. Structure-activity relationships (SARs), pharmacological 
      results, and docking studies indicated that the introduction of 5-methylthiazole 
      fragment to the five-atom moiety was beneficial for the activity. So far, the 
      existing data indicated that compound 12e may become a potential class II c-Met 
      inhibitor.
CI  - Copyright (c) 2020 American Chemical Society.
FAU - Zhang, Qian
AU  - Zhang Q
AD  - Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of 
      Pharmacy, Jiangxi Science & Technology Normal University, 605 Fenglin Road, 
      Nanchang, Jiangxi 330013, China.
FAU - Liu, Xiaobo
AU  - Liu X
AD  - Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of 
      Pharmacy, Jiangxi Science & Technology Normal University, 605 Fenglin Road, 
      Nanchang, Jiangxi 330013, China.
FAU - Gan, Wenhui
AU  - Gan W
AD  - Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of 
      Pharmacy, Jiangxi Science & Technology Normal University, 605 Fenglin Road, 
      Nanchang, Jiangxi 330013, China.
FAU - Wu, Jinjin
AU  - Wu J
AD  - Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of 
      Pharmacy, Jiangxi Science & Technology Normal University, 605 Fenglin Road, 
      Nanchang, Jiangxi 330013, China.
FAU - Zhou, Hualan
AU  - Zhou H
AD  - Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of 
      Pharmacy, Jiangxi Science & Technology Normal University, 605 Fenglin Road, 
      Nanchang, Jiangxi 330013, China.
FAU - Yang, Zunhua
AU  - Yang Z
AD  - College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 
      330004, China.
FAU - Zhang, Yiling
AU  - Zhang Y
AD  - College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 
      330004, China.
FAU - Liao, Min
AU  - Liao M
AD  - Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of 
      Pharmacy, Jiangxi Science & Technology Normal University, 605 Fenglin Road, 
      Nanchang, Jiangxi 330013, China.
FAU - Yuan, Ping
AU  - Yuan P
AD  - Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of 
      Pharmacy, Jiangxi Science & Technology Normal University, 605 Fenglin Road, 
      Nanchang, Jiangxi 330013, China.
FAU - Xu, Shan
AU  - Xu S
AD  - Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of 
      Pharmacy, Jiangxi Science & Technology Normal University, 605 Fenglin Road, 
      Nanchang, Jiangxi 330013, China.
FAU - Zheng, Pengwu
AU  - Zheng P
AD  - Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of 
      Pharmacy, Jiangxi Science & Technology Normal University, 605 Fenglin Road, 
      Nanchang, Jiangxi 330013, China.
FAU - Zhu, Wufu
AU  - Zhu W
AD  - Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of 
      Pharmacy, Jiangxi Science & Technology Normal University, 605 Fenglin Road, 
      Nanchang, Jiangxi 330013, China.
LA  - eng
PT  - Journal Article
DEP - 20200629
PL  - United States
TA  - ACS Omega
JT  - ACS omega
JID - 101691658
PMC - PMC7364574
COIS- The authors declare no competing financial interest.
EDAT- 2020/07/21 06:00
MHDA- 2020/07/21 06:01
PMCR- 2020/06/29
CRDT- 2020/07/21 06:00
PHST- 2020/02/25 00:00 [received]
PHST- 2020/06/19 00:00 [accepted]
PHST- 2020/07/21 06:00 [entrez]
PHST- 2020/07/21 06:00 [pubmed]
PHST- 2020/07/21 06:01 [medline]
PHST- 2020/06/29 00:00 [pmc-release]
AID - 10.1021/acsomega.0c00838 [doi]
PST - epublish
SO  - ACS Omega. 2020 Jun 29;5(27):16482-16490. doi: 10.1021/acsomega.0c00838. 
      eCollection 2020 Jul 14.