Molecular Design, Synthesis and Docking Study of Alkyl and Benzyl Derivatives of Robustic Acid as Topoisomerase I Inhibitors
Rui Chen
Institute of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530222 P. R. China
Faculty of Chinese Medicine Science, Guangxi University of Chinese Medicine, Nanning, 530222 P. R. China
These authors contributed equally to this work.
Search for more papers by this authorJiayong Huang
Institute of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530222 P. R. China
These authors contributed equally to this work.
Search for more papers by this authorYogini Jaiswal
Center for Excellence in Post-Harvest Technologies, North Carolina A&T State University, The North Carolina Research Campus, 500 Laureate Way, Kannapolis, NC-28081 USA
Search for more papers by this authorJianhua Wei
Institute of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530222 P. R. China
Search for more papers by this authorCorresponding Author
Lini Huo
Institute of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530222 P. R. China
Search for more papers by this authorXing Xia
Institute of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530222 P. R. China
Search for more papers by this authorJing Zhong
Institute of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530222 P. R. China
Search for more papers by this authorLeonard Williams
Center for Excellence in Post-Harvest Technologies, North Carolina A&T State University, The North Carolina Research Campus, 500 Laureate Way, Kannapolis, NC-28081 USA
Search for more papers by this authorMaochun Huang
Faculty of Chinese Medicine Science, Guangxi University of Chinese Medicine, Nanning, 530222 P. R. China
Search for more papers by this authorYan Liang
Guangxi Medical University, Nanning, 530021 P. R. China
Search for more papers by this authorRui Chen
Institute of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530222 P. R. China
Faculty of Chinese Medicine Science, Guangxi University of Chinese Medicine, Nanning, 530222 P. R. China
These authors contributed equally to this work.
Search for more papers by this authorJiayong Huang
Institute of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530222 P. R. China
These authors contributed equally to this work.
Search for more papers by this authorYogini Jaiswal
Center for Excellence in Post-Harvest Technologies, North Carolina A&T State University, The North Carolina Research Campus, 500 Laureate Way, Kannapolis, NC-28081 USA
Search for more papers by this authorJianhua Wei
Institute of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530222 P. R. China
Search for more papers by this authorCorresponding Author
Lini Huo
Institute of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530222 P. R. China
Search for more papers by this authorXing Xia
Institute of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530222 P. R. China
Search for more papers by this authorJing Zhong
Institute of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530222 P. R. China
Search for more papers by this authorLeonard Williams
Center for Excellence in Post-Harvest Technologies, North Carolina A&T State University, The North Carolina Research Campus, 500 Laureate Way, Kannapolis, NC-28081 USA
Search for more papers by this authorMaochun Huang
Faculty of Chinese Medicine Science, Guangxi University of Chinese Medicine, Nanning, 530222 P. R. China
Search for more papers by this authorYan Liang
Guangxi Medical University, Nanning, 530021 P. R. China
Search for more papers by this authorAbstract
Robustic acid is reported to be a bioactive compound, isolated from the medicinal plant Dalbergia benthamii Prain. Ten alkyl and benzyl derivatives (2a–2j) of robustic acid were designed and synthesized based on molecular docking approaches. The biological activities of most of the synthesized compounds (such as 2g, 2h, and 2i) were closely consistent with the docking results. In particular, 4-O-phenylpropyl substituted compound 2g displayed potent topoisomerase I inhibitory activity as well as cytotoxicity against SMMC-7721, HepG2, and HeLa cell lines. Further biological testing suggests that compound 2g acted mainly by an arrest of the tumor cells in G1 phase of the cell cycle and suppressed cell proliferation by inducing apoptosis. The findings of this study are encouraging with respect to potential utilization of these compounds as new topoisomerase I inhibitors.
Graphical Abstract
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