Synthesis, antiviral and contraceptive activities of nucleoside–sodium cellulose sulfate acetate and succinate conjugates

✍ Scribed by Hitesh K. Agarwal; Anil Kumar; Gustavo F. Doncel; Keykavous Parang

• Book ID: 104004964
• Publisher: Elsevier Science
• Year: 2010
• Tongue: English
• Weight: 297 KB
• Volume: 20
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/j.bmcl.2010.09.133

✦ Synopsis

Chemical conjugates between sodium cellulose sulfate (CS), displaying contraceptive and HIV-entry inhibiting properties, and nucleoside reverse transcriptase inhibitors (NRTIs) (3 0 -azido-2 0 ,3 0 -dideoxythymidine (AZT), 3 0 -fluoro-2 0 ,3 0 -dideoxythymidine (FLT), or 2 0 ,3 0 -dideoxy-3 0 -thiacytidine (3TC)) were designed to simultaneously provide contraceptive and anti-HIV activity. Two linkers, acetate and succinate, were used to conjugate the nucleoside analogs with CS. The conjugates containing cellulose sulfateacetate (CSA) (e.g., AZT-CSA and FLT-CSA) were found to be more potent than CS and other conjugates (e.g., AZT-succinate-CS, and FLT-succinate-CS). The presence of both sulfate and the acetate groups on cellulose were critical for generating maximum anti-HIV activity. In addition to showing equal potency against wild-type and multidrug resistant HIV-1, the AZT-CSA conjugate displayed significant contraceptive activity in an animal model, providing the initial proof-of-concept for the design and synthesis of dual-activity compounds based on these combinations.