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Evaluation of DNA Binding and Topoisomerase I Inhibitory Activities of 16’‐Decarbomethoxydihydrovoacamine from Tabernaemontana corymbosa
Author(s) -
Tan Chun Hoe,
Sim Dawn Su Yin,
Heng Mok Piew,
Lim Siew Huah,
Low Yun Yee,
Kam Toh Seok,
Sim Kae Shin
Publication year - 2020
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.202004153
Subject(s) - topoisomerase , cytotoxicity , dna , biochemistry , chemistry , dna supercoil , in vitro , pbr322 , mtt assay , stereochemistry , microbiology and biotechnology , biology , plasmid , dna replication
An iboga‐vobasine bisindole alkaloid, 16’‐decarbomethoxydihydrovoacamine ( 1 ) isolated from the stem bark extract of Tabernaemontana corymbosa exhibited strong cytotoxicity against colorectal cancer cell lines in our preliminary study. As an initial step to elucidate its anti‐proliferative mechanism, the DNA binding and topoisomerase I (topo1) inhibitory activities of the bisindole 1 were investigated. The results of the in vitro DNA binding studies and molecular docking calculations collectively suggested that 1 binds to the DNA minor groove via hydrophobic interactions with a binding constant ( K b ) of 7.40×10 5 M −1 . Treatment of Escherichia coli topo1 with 1 did not inhibit the enzyme from relaxing the supercoiled plasmid DNA pBR322, indicating that the cytotoxicity of 1 in colorectal cancer cells is independent of topo1. The bisindole is predicted to possess substantial bioavailability without major toxicity. Moreover, the cytotoxicity of 1 is selective towards the colorectal cancer cells as evaluated using the MTT assay.