Novel conjugates of podophyllotoxin and coumarin: Synthesis, cytotoxicities, cell cycle arrest, binding CT DNA and inhibition of Topo IIβ.
Basic Information
ID: ALA4433257
Journal: Bioorg Med Chem Lett
Title: Novel conjugates of podophyllotoxin and coumarin: Synthesis, cytotoxicities, cell cycle arrest, binding CT DNA and inhibition of Topo IIβ.
Authors: Hao SY, Feng SL, Wang XR, Wang Z, Chen SW, Hui L.
Abstract: A series of conjugates of podophyllotoxin and coumarin were prepared using the click reaction, and their cytotoxicities against A549, HepG2, HeLa, and LoVo cells were evaluated. Among them, compound 14e exhibited the strongest cytotoxicities against these cancer cells with IC50 values of 4.9-17.5 μM. Furthermore, 14e disrupted microtubules and induced cell cycle arrest at G1 phase by regulating P21 and Cyclin D1 in LoVo cells. In addition, 14e bond CT DNA and selectively inhibited Topo IIβ over Topo IIα. Molecular docking model showed that 14e appeared to form stable hydrogen bonds with several DNA bases and residue Gln778. Taken together, these conjugates have the potential to be developed as anti-tumor drugs.
CiteXplore: 31278032
DOI: 10.1016/j.bmcl.2019.06.063
Patent ID: ┄