Synthesis and γ-radiolysis of 2'-deoxy-5-fluorouridine and 5-fluorouridine derivatives

Article abstract of DOI:10.1002/jhet.5570290516

Seventeen compounds having a variety of substituents at the 3- and 5'-positions of 2'-deoxy-5-fluorouridine (5-FUdR) and 5-fluorouridine (5-FUR) were synthesizedd, and their γ-radiolysis in aqueous solutions were studied. The compounds having thioureido (RNHCSNH, R = H, PhCH₂, acyl) and thiocarbonylamino (XCSNH, X = PhCH₂S, PhO) groups at the 3-position of 5-FUdR were efficiently cleaved to give 5-FUdR with high G values upon γ-irradiation of their aqueous solutions. The active species for these cleavage reactions were hydrated electron (e^-(aq)), H^. and HO^.. However, the compounds having a dimethylsulfoxyimino group at 3-position of 5-FUdR and 5-FUR afforded 5-FUdR and 5-FUR only under the radiolysis conditions where e^-(aq) becomes a principal active species. The compound having a 2-benzoylthiazoylthiocarbonylamino group at the 3-position of 5-FUdR showed the highest reactivity toward HO^.. The mechanisms of these γ-radiolysis reactions are discussed. The examination of anticellular activities of γ-irradiated compounds having a thiocarbonylamino group at the 3-position of 5-FUdR toward murine Sarcoma 180 cells revealed that these compounds may be utilized as a candidate for a radiation-induced drug (RID).