Trachycladines and Analogues: Synthesis and Evaluation of Anticancer Activity.
The synthesis of four new analogues of marine nucleoside trachycladine A was accomplished by direct regio- and stereoselective Vorbrüggen glycosylations of 2,6-dichloropurine and 2-chloropurine with a d-ribose-derived chiron. Naturally occurring trachycladines A and B and a series of analogues were examined for their cytotoxic activity against a number of cancer cell lines (glioblastoma, lung, and cervical cancer). Parent trachycladine A and two analogues (the diacetate of the 2,6-dichloropurine derivative and N-cyclopropyl trachycladine A) resulted in a significant decrease in cell viability, with the latter exhibiting a stronger effect. The same compounds enhanced the cytotoxic effect of docetaxel in lung cancer cell lines, whereas additional experiments revealed that their mode of action relies on mitotic catastrophe rather than DNA damage. Moreover, their activity as autophagic flux blockers was postulated.
['Peitsinis|Zisis V|ZV|', 'Mitrakas|Achilleas G|AG|', 'Nakiou|Eirini A|EA|', 'Melidou|Dafni A|DA|', 'Kalamida|Dimitra|D|', 'Kakouratos|Christos|C|', 'Koukourakis|Michael I|MI|', 'Koumbis|Alexandros E|AE|']
D000970:Antineoplastic Agents D001343:Autophagy D045744:Cell Line, Tumor D002470:Cell Survival D004249:DNA Damage D006801:Humans D007211:Indoles D008856:Microscopy, Fluorescence D011687:Purines D013237:Stereoisomerism
trachycladines glycosylation mitotic catastrophe antitumor agents autophagy