Thiocarbamates as non-nucleoside HIV-1 reverse transcriptase inhibitors: docking-based CoMFA and CoMSIA analyses. 2009

Elena Cichero, and Sara Cesarini, and Paola Fossa, and Andrea Spallarossa, and Luisa Mosti
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Genova, Viale Benedetto XV n.3, 16132 - Genova. Italy.

Thiocarbamates (TCs) have been recently identified as a new class of potent non-nucleoside HIV-1 Reverse Transcriptase (RT) inhibitors. A computational strategy based on molecular docking studies, followed by CoMFA and CoMSIA analyses, has been used to elucidate the atomic details of the RT/TC interactions and to identify the most important features impacting the TC antiretroviral activity. The CoMFA model resulted to be the more predictive, and gave r(2)=0.93, r(cv)(2)=0.53, SEE=0.292, F=180, and r(test)(2)=0.70. The 3D-QSAR field contributions and the structural features of the RT binding site showed a good correlation. These studies will be useful to design new TCs with improved potency also against clinically relevant resistant mutants.

UI MeSH Term Description Entries
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
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
D013859 Thiocarbamates Carbamates in which the -CO- group has been replaced by a -CS- group. Thiocarbamate
D054303 HIV Reverse Transcriptase A reverse transcriptase encoded by the POL GENE of HIV. It is a heterodimer of 66 kDa and 51 kDa subunits that are derived from a common precursor protein. The heterodimer also includes an RNAse H activity (RIBONUCLEASE H, HUMAN IMMUNODEFICIENCY VIRUS) that plays an essential role the viral replication process. Reverse Transcriptase, HIV,Reverse Transcriptase, Human Immunodeficiency Virus,Transcriptase, HIV Reverse
D018894 Reverse Transcriptase Inhibitors Inhibitors of reverse transcriptase (RNA-DIRECTED DNA POLYMERASE), an enzyme that synthesizes DNA on an RNA template. Reverse Transcriptase Inhibitor,Inhibitors, Reverse Transcriptase,Inhibitor, Reverse Transcriptase,Transcriptase Inhibitor, Reverse

Related Publications

Elena Cichero, and Sara Cesarini, and Paola Fossa, and Andrea Spallarossa, and Luisa Mosti
July 2011, Journal of molecular modeling,
Elena Cichero, and Sara Cesarini, and Paola Fossa, and Andrea Spallarossa, and Luisa Mosti
May 2004, Journal of computer-aided molecular design,
Elena Cichero, and Sara Cesarini, and Paola Fossa, and Andrea Spallarossa, and Luisa Mosti
April 2012, Journal of molecular modeling,
Elena Cichero, and Sara Cesarini, and Paola Fossa, and Andrea Spallarossa, and Luisa Mosti
November 2017, Current medicinal chemistry,
Elena Cichero, and Sara Cesarini, and Paola Fossa, and Andrea Spallarossa, and Luisa Mosti
January 2011, Journal of molecular modeling,
Elena Cichero, and Sara Cesarini, and Paola Fossa, and Andrea Spallarossa, and Luisa Mosti
December 2013, Future medicinal chemistry,
Elena Cichero, and Sara Cesarini, and Paola Fossa, and Andrea Spallarossa, and Luisa Mosti
August 2008, Journal of chemical information and modeling,
Elena Cichero, and Sara Cesarini, and Paola Fossa, and Andrea Spallarossa, and Luisa Mosti
February 2019, Molecular diversity,
Elena Cichero, and Sara Cesarini, and Paola Fossa, and Andrea Spallarossa, and Luisa Mosti
December 2002, Proteins,
Elena Cichero, and Sara Cesarini, and Paola Fossa, and Andrea Spallarossa, and Luisa Mosti
February 2004, Journal of medicinal chemistry,
Copied contents to your clipboard!