Naslov
C-5 Hydroxyethyl and Hydroxypropyl Acyclonucleosides as Substrates for Thymidine Kinase of Herpes Simplex Virus Type 1 (HSV-1 TK): Syntheses and Biological Evaluation

Autori
Meščić, Andrijana ; Krištafor, Svjetlana ; Novaković, Ivana ; Osmanović, Amar ; Müller, Ursina ; Završnik, Davorka ; Ametamey, Simon M. ; Scapozza, Leonardo ; Raić-Malić, Silvana

Izvornik
Molecules (1420-3049) 18 (2013), 5; 5104-5124

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
acyclic nucleoside analogues ; 5-substituted pyrimidines ; herpes simplex virus type 1 thymidine kinase (HSV-1 TK) ; positron emission tomography (PET)

Sažetak
The efficient syntheses of 5-(2-hydroxyethyl)- and 5-(3-hydroxypropyl)-substituted pyrimidine derivatives bearing 2, 3-dihydroxypropyl, acyclovir-, ganciclovir- and penciclovir-like side chains are reported. A synthetic approach that included the alkylation of an N-anionic-5- substituted pyrimidine intermediate (method A) provided the target acyclonucleosides in significantly higher overall yields in comparison to those obtained by method B using sylilation reaction. The phosphorylation assays of novel compounds as potential substrates for thymidine kinase of herpes simplex virus type 1 (HSV-1 TK) showed that solely pyrimidine 5-substituted acyclonucleosides with a penciclovir-like side chain acted as a fraudulent substrates of HSV-1 TK. Moreover, the uracil derivative with penciclovir- like side chain with less bulky 2-hydroxyethyl substituent at C-5 proved to be a better substrate than the corresponding one with a 3-hydroxypropyl substituent. Therefore, this acyclonucleoside was selected as a lead compound for the development of a positron emission tomography HSV-1 TK activity imaging agent.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA