Abstract

HIGHLIGHTS

New 32 hexahydroquinoline (HHQ) analogues 6a–i, 8a–m, 10a–d, and 12a–f having the same features of EGFR inhibitors were synthesised in racemic mixtures.

The antiproliferative activities were assessed towards 60 cancer cell lines which were efficiently inhibited by compound 10c.

Compound 10d remarkably inhibited EGFRWT, EGFRT790M, and EGFRL858R.

Cell cycle analysis and Annexin V-based flow cytometry in the HOP-92 lung cancer cells were performed.

The safety profile of compounds 10c and 10d was validated using normal human lung (IMR-90) cells.

Molecular docking studies revealed that the S-isomers exhibited higher affinity than R-isomers to active sites.

Details

Title
Recruitment of hexahydroquinoline as anticancer scaffold targeting inhibition of wild and mutants EGFR (EGFRWT, EGFRT790M, and EGFRL858R)
Author
Abo Al-Hamd, Mahmoud G 1 ; Tawfik, Haytham O 1 ; Abdullah, Omeima 2 ; Yamaguchi, Koki 3 ; Sugiura, Masaharu 3 ; Mehany, Ahmed B M 4 ; El-Hamamsy, Mervat H 1 ; El-Moselhy, Tarek F 1 

1  Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Tanta University , Tanta , Egypt 
2  Pharmaceutical Chemistry Department, College of Pharmacy, Umm Al-Qura University , Makkah , Saudi Arabia 
3  Faculty of Pharmaceutical Sciences, Sojo University , Kumamoto , Japan 
4  Zoology Department, Faculty of Science, Al-Azhar University , Cairo , Egypt 
Publication year
2023
Publication date
Dec 2023
Publisher
Taylor & Francis Ltd.
ISSN
14756366
e-ISSN
14756374
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1080/14756366.2023.2241674
ProQuest document ID
2917549084
Copyright
© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.. This work is licensed under the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.