Please use this identifier to cite or link to this item:
http://cmuir.cmu.ac.th/jspui/handle/6653943832/74621
Title: | Design, synthesis and evaluation of novel dehydroabietic acid-dithiocarbamate hybrids as potential multi-targeted compounds for tumor cytotoxicity |
Authors: | Chengyang Ni Ya Ju Wu Mei Ran Jingyan Li Hong Li Cai Lan Jian Liu Ping Dai Jianming Wu Fangyao Li |
Authors: | Chengyang Ni Ya Ju Wu Mei Ran Jingyan Li Hong Li Cai Lan Jian Liu Ping Dai Jianming Wu Fangyao Li |
Keywords: | Chemical Engineering;Chemistry |
Issue Date: | 1-Oct-2022 |
Abstract: | In the present study, novel representatives of the important group of biologically-active, dehydroabietic acid-bearing dithiocarbamate moiety, were synthesized and characterized by 1H NMR, 13C NMR, HR-MS. The in vitro antiproliferative activity evaluation (MTT) indicated that these compounds exhibited potent inhibitory activities in various cancer cell lines (HepG-2, MCF-7, HeLa, T-24, MGC-803). Particularly, compound III-b possessed extraordinary cytotoxicity with low micromolar IC50 values ranging from 4.07 to 38.84 µM against tested cancer cell lines, while displayed weak cytotoxicity on two normal cell lines (LO-2 and HEK 293 T). Subsequently, the potential mechanisms of representative compound III-b were elementarily investigated by Transwell experiment, which showed III-b can inhibit cancer cells migration. Annexin-V/PI dual staining showed that the compound can induce HepG-2 cells apoptosis in a dose-dependent manner. Meanwhile this apoptosis may be related to the upregulated protein expression of cleaved-caspase 3, cleaved-caspase 9, Bax and downregulated of Bcl-2 indicated by Western Blot. Later study further confirmed that ROS levels in HepG-2 cells increased significantly with the rise of concentrations. In addition, through the network pharmacology data analyzing, the core targets and signaling pathways of compound III-b for treatment of liver neoplasms were forecasted. Molecular docking model showed that compound III-b had high affinity with hub targets (CASP3, EGFR, HSP90AA1, MAPK1, ERBB2, MDM2), suggesting that compound III-b might target the hub protein to modulate signaling activity. Taken together, these data indicated that dehydroabietic acid structural modification following the “Molecular hybridization” principle is a feasible way to discover the potential multi-targeted antitumor compounds. |
URI: | https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85135793968&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/74621 |
ISSN: | 18785352 |
Appears in Collections: | CMUL: Journal Articles |
Files in This Item:
There are no files associated with this item.
Items in CMUIR are protected by copyright, with all rights reserved, unless otherwise indicated.