RESUMO
The synthesis of four new analogues of marine nucleoside trachycladineâ 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 trachycladinesâ 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 trachycladineâ A and two analogues (the diacetate of the 2,6-dichloropurine derivative and N-cyclopropyl trachycladineâ 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.