Development of penipanoid C-inspired 2-benzoyl-1-methyl-2,3-dihydroquinazolin-4(1H)-one derivatives as potential EGFR inhibitors: Synthesis, anticancer evaluation and molecular docking study
- Authors
- Veena, K.; Raghu, M. S.; Kumar, K. Yogesh; Dahlous, Kholood A.; Bahajjaj, Aboud Ahmed Awadh; Mani, G.; Jeon, Byong-Hun; Prashanth, M. K.
- Issue Date
- Jun-2022
- Publisher
- ELSEVIER
- Keywords
- Quinazolin-4(1H)-one; Anticancer; Cytotoxicity; EGFR; Molecular docking
- Citation
- JOURNAL OF MOLECULAR STRUCTURE, v.1258, pp.1 - 9
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF MOLECULAR STRUCTURE
- Volume
- 1258
- Start Page
- 1
- End Page
- 9
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/170112
- DOI
- 10.1016/j.molstruc.2022.132674
- ISSN
- 0022-2860
- Abstract
- A novel class of penipanoid C-inspired 2-benzoyl-1-methyl-2,3-dihydroquinazolin-4(1H)-ones (3a-3f) and 1-methyl-2-(3,4,5-trihydroxybenzoyl)-2,3-dihydroquinazolin-4(1H)-one derivatives (10-15) was successfully synthesized using the I 2 /DMSO method. The newly synthesized compounds were characterized and tested for cytotoxicity against three cancer cell lines: HepG2 (human liver), MCF7 (human breast), and HCT116 (human colorectal). The majority of the tested molecules had a considerable cytotoxic impact, in some cases larger than doxorubicin. Furthermore, the inhibitory effect of six compounds (10-15) against epidermal growth factor receptor (EGFR) kinases were investigated, with three compounds (10, 11 and 12) showing good IC50 values. The IC50 values for compounds 10 and 12 against wildtype EGFR were 0.222 and 0.172 mu M, respectively. Compound 12 had good enzyme inhibitory efficacy with 71.30 and 421.53 mu M for the EGFR L858R and T790M mutants, respectively, which is more effective than the positive control, erlotinib, and close to lapatinib. The results of the biological screening were also confirmed by docking studies, which predicted the potential binding interactions of the target compounds with the EGFR active sites. Compounds 10 and 12 appear to be interesting lead compounds with the potential to be developed as anticancer agents, based on the findings.
- Files in This Item
-
Go to Link
- Appears in
Collections - 서울 공과대학 > 서울 자원환경공학과 > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/170112)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.