106636-74-2Relevant academic research and scientific papers
An efficient method for 4β-anilino-4'-demethylepipodophyllotoxins: Synthesis of NPF and W-68
Kamal,Gayatri
, p. 3359 - 3362 (1996)
4β-Substituted podophyllotoxin congeners have been obtained with significant stereoselectivity and improved yields by employing Bu4N+I in the displacement reaction of the 4-bromoepipodophyllotoxin. The DNA topoisomerase II inhibitors, NPF and W-68 have been prepared in good yields by this method.
A colon-targeted podophyllotoxin nanoprodrug: synthesis, characterization, and supramolecular hydrogel formation for the drug combination
Ha, Wei,Zhao, Xiao-Bo,Zhao, Wei-Hua,Tang, Jiang-Jiang,Shi, Yan-Ping
, p. 3200 - 3209 (2021/04/21)
Making full use of the undeveloped bioactive natural product derivatives by selectively delivering them to target sites can effectively increase their druggability and reduce the wastage of resources. Azo-based prodrugs are widely regarded as an effective targeted delivery means for colon-related disease treatment. Herein, we report a new-type of azo-based nanoprodrug obtained from bioactive natural products, in which the readily available podophyllotoxin natural products are connected with methoxy polyethylene glycol (mPEG)viaa multifunctional azobenzene group. The amphiphilic prodrug can form nanosized micelles in water and will be highly selectively activated by azoreductases, leading to thein situgeneration of anticancer podophyllotoxin derivatives (AdP) in the colon after the cleavage of the azo bond. To satisfy the demand of drug carriers for cancer combination therapy in clinics, α-CD is further introduced into this nanoprodrug micelle system to form a supramolecular hydrogelviaa cascade self-assembly strategy. Using imaging mass spectrometry (IMS), the colon-specific drug release ability of the hydrogel after oral administration is demonstrated at the molecular level. Finally, the nanoprodrug hydrogel is further used as a carrier to load a hydrophilic anti-cancer drug 5-FU during the hierarchical self-assembly process and to co-deliverAdPand 5-FU for the drug combination. The combination use ofAdPand 5-FU provides enhanced cytotoxicity which indicates a significant synergistic interaction. This work offers a new way to enhance the therapeutic effect of nanoprodrugsviadrug combination, and provides a new strategy for reusing bioactive natural products and their derivatives.
New compounds related to podophyllotoxin and congeners: synthesis, structure elucidation and biological testing.
Hansen,Jensen,Willumsen,Norskov-Lauritsen,Ebbesen,Nielsen,Buchardt
, p. 1190 - 1200 (2007/10/02)
4-Azido, 4-amino, 4-amido and 4-alkoxy compounds related to the lignans podophyllotoxin and 4'-demethylepipodophyllotoxin have been synthesized, and their structures elucidated. The Ritter reaction was shown to be useful in the preparation of the 4-amido compounds with the required stereochemistry. A preparative method for 4-chloro-4-deoxypicrophyllotoxin, for which all earlier synthetic attempts resulted in the two dehydrated compounds, alpha- and beta-apopicropodophyllotoxin, was developed. Supplementary preliminary studies of the biological activities of some of the compounds were performed. All compounds had pronounced inhibitory effect on the in vitro growth of human cervical cancer cells and TC-mouse cells with 4-amino-4-deoxypodophyllotoxin and 4-azido-4-deoxypodophyllotoxin showing the highest activity. Alkaline elution studies indicate that the toxicity of the 4'-demethoxy derivatives is due to protein-mediated DNA nicking. None of the compounds were found to have antiviral effect against herpes simplex type 2 (HSV-2), human immunodeficiency (HIV), and cytomegalovirus (CMV) in doses not toxic to the cells.
