Biomaterial Database

Synthesis, biological evaluation and molecular modeling studies of N-aryl-2-arylthioacetamides as non-nucleoside HIV-1 reverse transcriptase inhibitors. 2010

Zhu Xiaohe, and Qin Yu, and Yan Hong, and Song Xiuqing, and Zhong Rugang

College of Life Science and Bio-engineering, Beijing University of Technology, Pingleyuan Street No. 100, Chaoyang District, Beijing 100124, China.

A series of N-aryl-2-arylthioacetamide derivatives (2-4) designed as non-nucleoside reverse transcriptase inhibitors was synthesized and evaluated for their inhibitory activity against HIV-1 (IIIB) replication in MT-4 cell cultures. The compounds 2-4 were performed by the reaction of thiols and 2-chloro-N-substituted-acetamides and active in the lower micromolar concentration (1.25-20.83 μM). The studies of structure-activity relationship suggested that 1H-benzo[d]imidazole ring at arylthio moiety strongly improved the anti-HIV activity and consistent with the experimental data. The results of molecular modeling and docking within the RT non-nucleoside binding site using AutoDock confirmed that the 3 series, similar to other non-nucleoside reverse transcriptase inhibitors such as N-(5-chloro-2-pyridinyl)-N'-[2-(4-ethoxy-3-fluoro-2-pyridinyl)ethyl]-thiourea (PETT), was assumed in a butterfly-like conformation and helped to rationalize some SARs and the biological activity data.

UI	MeSH Term	Description	Entries
D007093	Imidazoles	Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
D008958	Models, Molecular	Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.	Molecular Models,Model, Molecular,Molecular Model
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D003198	Computer Simulation	Computer-based representation of physical systems and phenomena such as chemical processes.	Computational Modeling,Computational Modelling,Computer Models,In silico Modeling,In silico Models,In silico Simulation,Models, Computer,Computerized Models,Computer Model,Computer Simulations,Computerized Model,In silico Model,Model, Computer,Model, Computerized,Model, In silico,Modeling, Computational,Modeling, In silico,Modelling, Computational,Simulation, Computer,Simulation, In silico,Simulations, Computer
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001665	Binding Sites	The parts of a macromolecule that directly participate in its specific combination with another molecule.	Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D013844	Thiazoles	Heterocyclic compounds where the ring system is composed of three CARBON atoms, a SULFUR and NITROGEN atoms.	Thiazole
D013853	Thioacetamide	A crystalline compound used as a laboratory reagent in place of HYDROGEN SULFIDE. It is a potent hepatocarcinogen.	Thiacetamid,Thioacetamid
D014230	Triazoles	Heterocyclic compounds containing a five-membered ring with two carbon atoms and three nitrogen atoms with the molecular formula C2H3N3.	Triazole