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Diversity‐Oriented Synthesis of Diol‐Based Peptidomimetics as Potential HIV Protease Inhibitors and Antitumor Agents
Author(s) -
Vadhadiya Paresh M.,
Jean MarcAlexandre,
Bouzriba Chahrazed,
Tremblay Thomas,
Lagüe Patrick,
Fortin Sébastien,
Boukouvalas John,
Giguère Denis
Publication year - 2018
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201800247
Subject(s) - peptidomimetic , protease , hiv 1 protease , docking (animal) , chemistry , combinatorial chemistry , human immunodeficiency virus (hiv) , stereochemistry , diol , enzyme , biochemistry , biology , virology , organic chemistry , medicine , peptide , nursing
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.