[Pseudo-furocoumarin: synthesis, DNA-binding behavior and cytotoxicity].
Furocoumarin shows some antitumor activity when it is radiated by the UV light. In order to improve the antitumor activity of furocoumarin under standard environment conditions, the "minimal DNA-intercalating" hypothesis was firstly introduced to the structural modification of furocoumarin, which resulted in the design of pseudo-furocoumarin. The pseudo-furocoumarin was synthesized by two-step reaction including Pechmann reaction catalyzed by conc. H2SO4 and Suzuki coupling reaction catalyzed by Pd(PPh3)4. The structural character of the pseudo-furocoumarin is that the bonding mode of furan ring fused to the coumarin is replaced by a chemical single bond between furan ring and coumarin. The interaction of the pseudo-furocoumarin with calf thymus DNA (CT-DNA) has been respectively investigated by using DNA melting curve, UV-Vis absorption spectra, fluorescence spectra and viscosity titration, and the modes of DNA-binding for the pseudo-furocoumarin have been proposed. Based on the results of DNA melting curve, spectra and viscosity titration, it was suggested that 5a and 5b bind to DNA by the partial intercalation and classical intercalation, respectively. The DNA-binding behaviors of 5c and 5d have been rarely reported in literature and may be interpreted in terms of bridge-structure. All target compounds, except 5b, show a decreasing capability of intercalation to DNA. Further, the antiproliferative activities of the pseudo-furocoumarin on human lung adenocarcinoma (A549), human breast cancer (MCF-7) and human ovarian carcinoma cell line (SKOV-3) in vitro were evaluated using the sulforhodamine B (SRB) protein statin assay. All pseudo-furocoumarin exhibited an improved anti-proliferative activity as compared with the control compound psoralen (PS, a linear furocoumarin). Interestingly the pseudo-furocoumarin binding to DNA by a non-classical intercalation mode showed a stronger anti-proliferative activity than PS. The present study extended the applied areas of "minimal DNA-intercalating" hypothesis, and provided a method for the structural modification of furocoumarin as well.
Li-Juan
LJ
Xie
Zhuo
Z
Chen
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D002417:Cattle; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry*; D011564:Furocoumarins / Q000737:chemistry*; D006801:Humans; D007364:Intercalating Agents / Q000737:chemistry*; D014466:Ultraviolet Rays
D000970:Antineoplastic Agents; D011564:Furocoumarins; D007364:Intercalating Agents; D004247:DNA; C427203:calf thymus DNA