title: Indole-based allosteric inhibitors of HIV-1 integrase.
abstract: Employing a scaffold hopping approach, a series of allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) have been synthesized based on an indole scaffold. These compounds incorporate the key elements utilized in quinoline-based ALLINIs for binding to the IN dimer interface at the principal LEDGF/p75 binding pocket. The most potent of these compounds displayed good activity in the LEDGF/p75 dependent integration assay (IC50=4.5μM) and, as predicted based on the geometry of the five- versus six-membered ring, retained activity against the A128T IN mutant that confers resistance to many quinoline-based ALLINIs.
authors: Division of Medicinal Chemistry & Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, United States; Department of Chemistry, The Ohio State University, Columbus, OH 43210, United States.
authors: Pratiq A
authors: PA
authors: Patel
authors: Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH 43210, United States.
authors: Nina
authors: N
authors: Kvaratskhelia
authors: Division of Medicinal Chemistry & Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, United States; Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Helwan University, Cairo, Egypt.
authors: Yara
authors: Y
authors: Mansour
authors: Division of Medicinal Chemistry & Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, United States.
authors: Janet
authors: J
authors: Antwi
authors: Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH 43210, United States.
authors: Lei
authors: L
authors: Feng
authors: Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH 43210, United States.
authors: Pratibha
authors: P
authors: Koneru
authors: Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH 43210, United States.
authors: Mathew J
authors: MJ
authors: Kobe
authors: Division of Medicinal Chemistry & Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, United States.
authors: Nivedita
authors: N
authors: Jena
authors: Division of Medicinal Chemistry & Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, United States.
authors: Guqin
authors: G
authors: Shi
authors: Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Helwan University, Cairo, Egypt.
authors: Mosaad S
authors: MS
authors: Mohamed
authors: Division of Medicinal Chemistry & Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, United States.
authors: Chenglong
authors: C
authors: Li
authors: Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH 43210, United States. Electronic address: jacques.kessl@usm.edu.
authors: Jacques J
authors: JJ
authors: Kessl
authors: Division of Medicinal Chemistry & Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, United States. Electronic address: fuchs.42@osu.edu.
authors: James R
authors: JR
authors: Fuchs
mesh_terms: D000494:Allosteric Regulation; D018360:Crystallography, X-Ray; D019427:HIV Integrase / Q000187:drug effects*; D019428:HIV Integrase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006860:Hydrogen Bonding; D007211:Indoles / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D019428:HIV Integrase Inhibitors; D007211:Indoles; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1
keywords: ALLINI; HIV integrase inhibitor; Scaffold hopping