title: Synthesis and biological evaluation of new simple indolic non peptidic HIV Protease inhibitors: the effect of different substitution patterns.
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.
authors: Dipartimento di Scienze, Università degli studi della Basilicata, Viale dell'Ateneo Lucano 10, 85100 Potenza, Italy. Electronic address: carloc.bonini@libero.it.
authors: C
authors: C
authors: Bonini
authors: Dipartimento di Scienze, Università degli studi della Basilicata, Viale dell'Ateneo Lucano 10, 85100 Potenza, Italy.
authors: L
authors: L
authors: Chiummiento
authors: Dipartimento di Scienze, Università degli studi della Basilicata, Viale dell'Ateneo Lucano 10, 85100 Potenza, Italy.
authors: N
authors: N
authors: Di Blasio
authors: Dipartimento di Scienze, Università degli studi della Basilicata, Viale dell'Ateneo Lucano 10, 85100 Potenza, Italy.
authors: M
authors: M
authors: Funicello
authors: Dipartimento di Scienze, Università degli studi della Basilicata, Viale dell'Ateneo Lucano 10, 85100 Potenza, Italy.
authors: P
authors: P
authors: Lupattelli
authors: Dipartimento di Scienze, Università degli studi della Basilicata, Viale dell'Ateneo Lucano 10, 85100 Potenza, Italy.
authors: F
authors: F
authors: Tramutola
authors: Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Trieste, via Giorgieri 1, 34127 Trieste, Italy.
authors: F
authors: F
authors: Berti
authors: Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Trieste, via Giorgieri 1, 34127 Trieste, Italy.
authors: A
authors: A
authors: Ostric
authors: International Centre for Applied Research and Sustainable Technology, Bratislava SK-8410, Slovakia; University of SS. Cyril & Methodius, Faculty of Natural Sciences, Trnava, Slovakia.
authors: S
authors: S
authors: Miertus
authors: International Centre for Applied Research and Sustainable Technology, Bratislava SK-8410, Slovakia; Department of Physical Chemistry of Drugs, Faculty of Pharmacy, Comenius University, Bratislava SK-83232, Slovakia.
authors: V
authors: V
authors: Frecer
authors: ICS-UNIDO, Area Science Park, Trieste, Italy; State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China.
authors: D-X
authors: DX
authors: Kong
mesh_terms: D004305:Dose-Response Relationship, Drug; D016333:HIV Protease / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides; D013329:Structure-Activity Relationship
chemical_list: D017320:HIV Protease Inhibitors; D007211:Indoles; D010455:Peptides; C030374:indole; D016333:HIV Protease
keywords: HIV PR inhibitors; Indoles; Non-peptidic inhibitors