Synthesis and in vitro antitumour activity of crassalactone D, its stereoisomers and novel cinnamic ester derivatives

Abstract

Naturally occurring styryl lactone, crassalactone D (1), unnatural 4-epi-crassalactone D (2), and the corresponding 7-epimers (3 and 4) have been synthesized starting from d-glucose. The key step of the synthesis is a new one-pot sequence that commenced with a Z-selective Wittig olefination of suitably functionalized sugar lactols with a stabilized ylide, (methoxycarbonylmethylene)-triphenylphosphorane, in dry methanol, to afford 1 or 3, in the mixtures with the corresponding 4-epimers (2 or 4, respectively). A number of 6-O-cinnamoyl derivatives of styryl lactones 1-4 have been prepared, bearing electron donating or electron withdrawing functionalities in the C-4 position of cinnamic acid residue. The synthesized products were evaluated for their in vitro antiproliferative activity against selected human tumour cell lines, whereupon very potent cytotoxicities have been recorded in many cases. SAR analysis indicated some important structural features responsible for biological activity, such as stereochemistry at the C-4 and C-7 positions, as well as the nature of a substituent at the C-4 position in the aromatic ring of cinnamoate moiety. Flow cytometry and Western blot analysis data gave insight in the mechanism underlying antiproliferative effects of the synthesized compounds.

Evaluation of the influence of mirabilite on the absorption and pharmacokinetics of the ingredients in Dahuang‐mudan decoction by a validated UPLC/QTOF–MS/MS method

“…The results showed that 20 constituents of DMD were found in the plasmas of MDMD‐treated rats and NMDMD‐treated rats. Furthermore, more bioactive constituents were found in plasma of MDMD‐treated rats than in NMDMD‐treated rats, and these compounds may be considered potential effective constituents in DMD because they have extensive activities, such as hydroxybenzoic acid (3), which has antioxidant activity (Siao et al, ); cinnamoyl glucose (21), which possesses antitumor and anti‐inflammatory activity (Kovacevic et al, ); benzoyloxy paeoniflorin (37), which has proven antioxidant activity (Ryu et al, ); and hydroxy physcion (57) and rhein‐8 ‐O‐ glucopyranoside (20), which have been reported to ameliorate lung inflammatory responses (Kwon et al, ). The results showed that mirabilite could influence the absorption of some bioactive constituents in DMD.…”

Novel O-methyl goniofufurone and 7-epi-goniofufurone derivatives: synthesis, in vitro cytotoxicity and SAR analysis

“…To a cooled (0°C) and stirred solution of 12,16,11,21,23,25 or 28 (1 equiv.) in dry DMF (0.05 M) was added NaH (3.0-5.0 equiv.)…”

“…The cell cycle analysis was carried out following a previously reported procedure. 21 Detection of apoptosis. Apoptosis of K562 cells was evaluated according to a previously reported procedure.…”

“…Apoptosis of K562 cells was evaluated according to a previously reported procedure. 21 Western blot. Western blot was carried out as reported previously.…”

Chromatographic lipophilicity and pharmacokinetic behavior of some newly synthesized styryl lactone stereoisomers

“…The synthetic chemist today have an essential role to play in the development of efficient syntheses of these compounds and their analogues, to optimize the biological activity. A large number of styryl lactone derivatives have been synthesized and evaluated for their cytotoxicity against different human malignant cell lines (4)(5)(6)(7)(8)(9)(10). Many of the synthesized styryl lactones exhibited strong citotoxic activity.…”