Synthesis and Primary Evaluation of Novel HIV-1 Inhibitors

• Published in: Nucleosides, nucleotides & nucleic acids Vol. 26; no. 8-9; pp. 1161 - 1165
• Main Authors: El Safadi, Yazan, Marquet, Roland, Aubertin, Anne-Marie, Vivet-Boudou, Valérie
• Format: Journal Article
• Language: English
• Published: PHILADELPHIA Taylor & Francis Group 01.01.2007; Taylor & Francis
• Subjects: Anti-HIV Agents - chemical synthesis; Anti-HIV Agents - chemistry; Anti-HIV Agents - pharmacology; antiviral drug resistance; Biochemistry & Molecular Biology; Cellular Biology; Deoxyadenosines - chemical synthesis; Deoxyadenosines - chemistry; Deoxyadenosines - pharmacology; Drug Design; Drug Resistance, Viral - genetics; HIV-1; HIV-1 - drug effects; HIV-1 - genetics; HIV-1 - physiology; Human immunodeficiency virus 1; Humans; Life Sciences; Life Sciences & Biomedicine; Microbial Sensitivity Tests; Science & Technology; viral error catastrophe; Virus Replication - drug effects; HIV-1; MUTAGENESIS; antiviral drug resistance; viral error catastrophe; NUCLEOSIDES
• ISSN: 1525-7770; 1532-2335
• DOI: 10.1080/15257770701527109

The overcoming of antiviral drug resistance is an important challenge in the treatment of HIV-1 infection. According to the theory of viral error catastrophe, slightly increasing the mutation rate could exceed the error threshold for viability of a viral population and kill it. Investigation of this mechanism could lead to the discovery of new antiviral agents capable of bypassing viral resistance. To this aim, we designed several modified nucleosides. We describe here the synthesis and partial evaluation of 8-amido-2′-deoxyadenosine. The supplementary amide group on the base should allow base-pairing with several natural nucleosides, thus creating supplementary mutations that would kill the virus.