Naslov
Novel 1, 2, 4-triazole and purine acyclic cyclopropane nucleoside analogues: synthesis, antiviral and cytostatic activity evaluations

Autori
Benci, Krešimir ; Suhina, Tomislav ; Mandić, Leo ; Kraljević Pavelić, Sandra ; Tomljenović Paravić, Andrea ; Pavelić, Krešimir ; Balzarini, Jan ; Wittine, Karlo ; Mintas, Mladen

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Abstracts of the International Symposium on Advances in Synthetic and Medicinal Chemistry / Nicolaou, Kyriacos Costa - Sankt Peterburg, 2011, 221-230

Skup
International Symposium on Advances in Synthetic and Medicinal Chemistry

Mjesto i datum
Sankt Peterburg, Ruska Federacija, 21.08.2011. - 25.08.2011

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
synthesis; antiviral activity evaluations; Nucleoside analogues

Sažetak
Several published studies indicate that the acyclic guanine nucleoside analogues possessing bis(1, 2- hydroxymethyl) substituted cyclopropane rings mimicking the sugar moiety are potent inhibitors of replication of several herpes viruses. Established synthetic methods and antiviral and cytostatic activity assays were used for the evaluation of new 1, 2, 4-triazole and purine acyclic nucleoside analogues. The synthesis of new types of acyclic nucleoside analogues which incorporate 1, 2, 4-triazole (9–11 and 13) or purine (12 and 14–17) moiety bound via flexible methylenic spacer to the bis(1, 2-hydroxymethyl) cyclopropane ring. None of the new compounds showed pronounced antiviral activities at subtoxic concentrations on a broad panel of DNA and RNA viruses. Evaluation of their affinity for herpes simplex type 1 (HSV-1) and varicella-zoster virus-encoded thymidine kinases (VZV TK) also showed that none of the compounds was able to significantly inhibit 1 μM deoxythymidine phosphorylation by HSV-1 and VZV TK at 500 μM concentrations. The in vitro cytostatic activity evaluation results indicated a weak antiproliferative activity for all tested compounds. Only 6-pyrrolylpurine derivative bearing a carboxylic group substituted cyclopropane ring (17) produced a rather slight inhibitory effect at higher micromolar concentrations on a breast carcinoma cell line (MCF-7) and no cytotoxic effect on human normal fibroblasts (WI 38). The lack of antiherpetic activity may be due to poor, if any, recognition of the compounds by the virus-induced nucleoside kinases and to become metabolically activated.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA