Synthesis, Antiviral and Contraceptive Activities of Nucleoside-Sodium Cellulose Sulfate Acetate and Succinate Conjugates

Authors

Hitesh K. Agarwal, University of Rhode IslandFollow
Anil Kumar, Birla Institute of Technology & ScienceFollow
Gustavo F. Doncel, Eastern Virginia Medical School
Keykavous Parang, Chapman UniversityFollow

Document Type

Article

Publication Date

2010

Abstract

Chemical conjugates between sodium cellulose sulfate (CS), displaying contraceptive and HIV-entry inhibiting properties, and nucleoside reverse transcriptase inhibitors (NRTIs) (3′-azido-2′,3′-dideoxythymidine (AZT), 3′-fluoro-2′,3′-dideoxythymidine (FLT), or 2',3'-dideoxy-3'-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 sulfate-acetate (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.

Comments

NOTICE: this is the author’s version of a work that was accepted for publication in Bioorganic & Medicinal Chemistry Letters. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Bioorganic & Medicinal Chemistry Letters, volume 20, issue 23, in 2010. DOI: 10.1016/j.bmcl.2010.09.133

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Recommended Citation

Agarwal, Hitesh K., et al. "Synthesis, antiviral and contraceptive activities of nucleoside–sodium cellulose sulfate acetate and succinate conjugates." Bioorganic & medicinal chemistry letters 20.23 (2010): 6993-6997. DOI: 10.1016/j.bmcl.2010.09.133

Copyright

Elsevier

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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.