title: Synthesis of novel 2',3'-didehydro-2',3'-dideoxyinosine phosphoramidate prodrugs and evaluation of their anticancer activity.
abstract: An efficient synthesis of 4-chlorophenyl N-alkyl phosphoramidates of 2 ',3 '-didehydro-2 ',3 '-dideoxyinosine employing 4-chlorophenyl phosphoroditetrazolide as a phosphorylating agent is reported. Improved method for the synthesis of 2 ',3 '-didehydro-2 ',3 '-dideoxyinosine starting from inosine is also described. The synthesized phosphoramidates 11-18 were examined for their cytotoxic activity in three human cancer cell lines: cervical (HeLa), oral (KB), and breast (MCF-7) employing sulforhodamine B assay. The highest activity in all investigated cancer cell lines was displayed by phosphoramidate 13 with N-n-propyl substituent.
authors.affiliation: a Faculty of Chemistry , Adam Mickiewicz University , Grunwaldzka St 6, 60-780 Poznań , Poland.
authors.forename: Weronika
authors.initials: W
authors.lastname: Borek
authors.forename: Marta
authors.initials: M
authors.lastname: Lewandowska
authors.forename: Natalia
authors.initials: N
authors.lastname: Kleczewska
authors.forename: Piotr
authors.initials: P
authors.lastname: Ruszkowski
authors.forename: Karol
authors.initials: K
authors.lastname: Kacprzak
authors.forename: Lech
authors.initials: L
authors.lastname: Celewicz
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D016049:Didanosine / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D011355:Prodrugs; D016049:Didanosine
keywords: 2′,3′-didehydro-2′,3′-dideoxyinosine; Phosphorylation; anticancer activity; phosphoramidate; prodrug