title: Trachycladines and Analogues: Synthesis and Evaluation of Anticancer Activity.
abstract: 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.
authors.affiliation: Laboratory of Organic Chemistry, Department of Chemistry, Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece.
authors.forename: Zisis V
authors.initials: ZV
authors.lastname: Peitsinis
authors.affiliation: Department of Radiotherapy and Oncology, Radiobiology and Radiopathology Unit, Medical School, Democritus University of Thrace, 68100, Alexandroupolis, Greece.
authors.forename: Achilleas G
authors.initials: AG
authors.lastname: Mitrakas
authors.affiliation: Laboratory of Organic Chemistry, Department of Chemistry, Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece.
authors.forename: Eirini A
authors.initials: EA
authors.lastname: Nakiou
authors.affiliation: Laboratory of Organic Chemistry, Department of Chemistry, Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece.
authors.forename: Dafni A
authors.initials: DA
authors.lastname: Melidou
authors.affiliation: Department of Radiotherapy and Oncology, Radiobiology and Radiopathology Unit, Medical School, Democritus University of Thrace, 68100, Alexandroupolis, Greece.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Kalamida
authors.affiliation: Department of Radiotherapy and Oncology, Radiobiology and Radiopathology Unit, Medical School, Democritus University of Thrace, 68100, Alexandroupolis, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Kakouratos
authors.affiliation: Department of Radiotherapy and Oncology, Radiobiology and Radiopathology Unit, Medical School, Democritus University of Thrace, 68100, Alexandroupolis, Greece.
authors.forename: Michael I
authors.initials: MI
authors.lastname: Koukourakis
authors.affiliation: Laboratory of Organic Chemistry, Department of Chemistry, Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece.
authors.forename: Alexandros E
authors.initials: AE
authors.lastname: Koumbis
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D001343:Autophagy / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D008856:Microscopy, Fluorescence; D011687:Purines / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011687:Purines; C000620828:trachycladine A; C000620829:trachycladine B; C031268:2,6-dichloropurine
keywords: antitumor agents; autophagy; glycosylation; mitotic catastrophe; trachycladines