Diversity‐Oriented Synthesis of Diol‐Based Peptidomimetics as Potential HIV Protease Inhibitors and Antitumor Agents |
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| Authors: | Dr. Paresh M. Vadhadiya Dr. Marc‐Alexandre Jean Chahrazed Bouzriba Thomas Tremblay Dr. Patrick Lagüe Dr. Sébastien Fortin Dr. John Boukouvalas Dr. Denis Giguère |
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| Affiliation: | 1. Département de Chimie, Université Laval—RQRM, Quebec City, QC, Canada;2. CHU de Québec–Université Laval Research Center, Oncology Division, H?pital Saint-Fran?ois d'Assise, Quebec City, QC, Canada;3. Faculté de Pharmacie, Université Laval, Quebec City, QC, Canada;4. Départment de Biochimie, de Microbiologie et de Bio-Informatique, Université Laval, Quebec City, QC, Canada |
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| Abstract: | Peptidomimetic HIV protease inhibitors are an important class of drugs used in the treatment of AIDS. The synthesis of a new type of diol‐based peptidomimetics is described. Our route is flexible, uses d ‐glucal as an inexpensive starting material, and makes minimal use of protection/deprotection cycles. Binding affinities from molecular docking simulations suggest that these compounds are potential inhibitors of HIV protease. Moreover, the antiproliferative activities of compounds 33 a , 35 a , and 35 b on HT‐29, M21, and MCF7 cancer cell lines are in the low micromolar range. The results provide a platform that could facilitate the development of medically relevant asymmetrical diol‐based peptidomimetics. |
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| Keywords: | antitumor agents carbohydrates diversity-oriented synthesis peptidomimetics protease inhibitors |
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