Synthesis and biological evaluation of new simple indolic non peptidic HIV Protease inhibitors: The effect of different substitution patterns |
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| Affiliation: | 1. Dipartimento di Scienze, Università degli studi della Basilicata, Viale dell’Ateneo Lucano 10, 85100 Potenza, Italy;2. Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Trieste, via Giorgieri 1, 34127 Trieste, Italy;3. International Centre for Applied Research and Sustainable Technology, Bratislava SK-8410, Slovakia;4. University of SS. Cyril & Methodius, Faculty of Natural Sciences, Trnava, Slovakia;5. Department of Physical Chemistry of Drugs, Faculty of Pharmacy, Comenius University, Bratislava SK-83232, Slovakia;6. ICS-UNIDO, Area Science Park, Trieste, Italy;7. State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China;1. Department of Chemistry, Northern Kentucky University, Nunn Drive, Highland Heights, KY 41099, United States;2. Department of Chemistry, University of Cincinnati, Cincinnati, OH 45221, United States;1. Division of Pharmaceutical Sciences, University of Wisconsin-Madison, Madison, WI 53705, USA;2. Department of Chemistry, The Scripps Research Institute, 130 Scripps Way, #3A1, Jupiter, FL 33458, USA;3. Department of Cancer Biology, The Scripps Research Institute, Jupiter, FL 33458, USA;4. Department of Molecular Therapeutics, The Scripps Research Institute, 130 Scripps Way, #3A1, Jupiter, FL 33458, USA;5. Natural Products Library Initiative, The Scripps Research Institute, 130 Scripps Way, #3A1, Jupiter, FL 33458, USA;1. Key Laboratory on Luminescence and Real-Time Analysis (Ministry of Education), College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China;2. State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400715, China;3. School of Life Sciences, Southwest University, Chongqing 400715, China;4. Tibetan Collaborative Innovation Center of Agricultural and Animal Husbandry Resources, Agriculture and Animal Husbandry College, Tibet University, Nyingchi, Tibet 860000, China;1. Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan;2. Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan;3. Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Kho-Hong, Hat Yai, Songkhla 90112, Thailand;4. Department of Chemistry, Faculty of Science, Ochanomizu University, 2-1-1 Otsuka, Bunkyo-ku, Tokyo 112-8610, Japan |
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| Abstract: | New structurally simple indolic non peptidic HIV Protease inhibitors were synthesized from (S)-glycidol by regioselective methods. Following the concept of targeting the protein backbone, different substitution patterns were introduced onto the common stereodefined isopropanolamine core modifying the type of functional group on the indole, the position of the functional group on the indole and the type of the nitrogen containing group (sulfonamides or perhydroisoquinoline), alternatively. The systematic study on in vitro inhibition activity of such compounds confirmed the general beneficial effect of the 5-indolyl substituents in presence of arylsulfonamide moieties, which furnished activities in the micromolar range. Preliminary docking analysis allowed to identify several key features of the binding mode of such compounds to the protease. |
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| Keywords: | HIV PR inhibitors Non-peptidic inhibitors Indoles |
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