Synthesis and Biological Evaluation of New 4β-5-Fu-substituted 4'-Demethylepipodophyllotoxin Derivatives

Abstract

A series of new 4β-5-Fu-substituted 4 ' -demethylepipodophyllotoxin derivatives were synthesized and evaluated, together with some previously prepared ones, for their cytotoxic activities against four tumor cell lines (HL60, P388, A549 and BEL7402). Three of these compounds exhibited superior in vitro anticancer activity against P388 and A549 than the reference compound etoposide. In addition, the partition coefficients (P) of all the new and previously synthesized derivatives were determined.

A novel biotransformation process of 4′-demethylepipodophyllotoxin to 4′-demethylepipodophyllic acid by Bacillus fusiformis CICC 20463, Part II: process optimization

“…However, DMEP failed to move forward in human clinical trials because of unacceptable gastrointestinal toxic side-effects and low solubility [13][14][15]. Recently, DMEP becomes more and more commercially important as raw material for the semi-synthesis of anticancer drugs because of its structure similarity to Etoposide, which is one of the most prescribed anticancer drugs [16][17][18][19][20]. Numerous structural modifications of DMEP have been carried out in order to obtain derivatives which have been demonstrated to significant activity and high solubility [21][22][23].…”

A fragmentation study of podophyllotoxin and its 4′‐demethyl‐4β‐substituted derivatives by electrospray ionization ion‐trap time‐of‐flight tandem mass spectrometry

“…The novel synthetic compounds 2-4 are excellent examples of 4 0 -demethyl-4b-substituted derivatives of compound 1, whose syntheses have been the focus of attention over the last 20 years. [9][10][11][12] To our knowledge, this is the first report of the complete characterization of the fragmentation of this type of compounds using ESI-IT-TOF tandem mass spectrometry (MS [1][2][3][4][5][6][7][8][9] ) with accurate mass measurements.…”

“…[1][2][3][4] There is therefore widespread interest in the synthesis and properties of these natural compounds. [5][6][7][8][9][10][11][12] Furthermore, there is a need to establish reliable methods for their analysis and characterization. Mass spectrometry (MS) is one of the best techniques for this purpose, because it allows fast acquisition of full spectra with high sensitivity, and is easily coupled with separating techniques such as gas chromatography (GC) and liquid chromatography (LC).…”

Intérêt des lignanes dans la prévention et le traitement de cancers

“…Les modifications portent essentiellement sur les substituants du noyau E, qui détermi-nent l'interaction avec la TopIIα et les substituants du C 4 du noyau C qui influencent plutôt la disponibilité cellulaire [39]. Certains composés tels que le TOP-53 et le GL-331 ( Figure 1C) font actuellement l'objet de tests cliniques [40]. Les travaux récents d'Azarova et al [29] ont démontré que les leucémies secondaires aigües induites par l'étoposide impliquaient préférentiellement la formation de complexes SYNTHÈSE REVUES Figure 4.…”