Design of benzene-1,2-diamines as selective inducible nitric oxide synthase inhibitors: a combined de novo design and docking analysis

Journal of Molecular Modeling
Sandrea M FrancisPrasad V Bharatam

Abstract

Selective inhibition of inducible nitric oxide synthases (iNOS) has been a challenging problem for researchers pursuing work in finding methods to treat inflammatory disorders, shock, etc. Though many inhibitors have been studied to date, all are associated with selectivity or potency problems. Additionally, most of the reported compounds have several similarities and fewer number of novel structures are being tried. There is an increasing need to design novel molecules for this target. In this work, de novo design using LUDI, combined with docking analysis using FlexX has been employed in an attempt to identify novel scaffolds. Benzene-1,2-diamines were identified which could mimic the interactions of the substrate analogs and other inhibitors. Comparative docking scores in each of the isoforms of nitric oxide synthase were employed to recognize hits for iNOS selectivity.

References

Oct 27, 1995·Journal of Medicinal Chemistry·J F KerwinP L Feldman
Mar 1, 1994·The Biochemical Journal·R G Knowles, S Moncada
Jun 24, 1994·Journal of Medicinal Chemistry·M A Marletta
Nov 11, 1994·Journal of Medicinal Chemistry·W M MooreM G Currie
Jan 1, 1995·British Journal of Pharmacology·G J SouthanC Thiemermann
Mar 16, 1993·European Journal of Pharmacology·T P MiskoM G Currie
Aug 23, 1996·Journal of Molecular Biology·M RareyG Klebe
May 23, 1998·Journal of Medicinal Chemistry·D W HansenB S Pitzele
Sep 11, 1998·Journal of Medicinal Chemistry·T J HagenE A Hallinan
Aug 28, 1999·The Journal of Biological Chemistry·B R BabuO W Griffith
Feb 7, 2001·Biochemical and Biophysical Research Communications·M NakaN Taniguchi
May 1, 2001·Bioorganic & Medicinal Chemistry Letters·H BeatonA V Wallace
Jul 21, 2001·The Biochemical Journal·W K AldertonR G Knowles
Jan 29, 2002·Current Pharmaceutical Design·L SalernoM A Siracusa
Dec 31, 2003·Bioorganic & Medicinal Chemistry Letters·Shigeo UedaMotoji Kawasaki
Apr 9, 2004·Proceedings of the National Academy of Sciences of the United States of America·Roman FedorovIlme Schlichting
May 11, 2004·Chemical & Pharmaceutical Bulletin·Shigeo UedaMotoharu Ido
Dec 16, 2004·Journal of Inorganic Biochemistry·Huiying Li, Thomas L Poulos
Oct 13, 2006·Journal of Medicinal Chemistry·Haitao JiRichard B Silverman
Mar 14, 2007·Journal of Molecular Graphics & Modelling·V AparnaB Gopalakrishnan

❮ Previous
Next ❯

Citations

Apr 28, 2011·Journal of Molecular Modeling·Xiu-Long ShenQing-Zhi Gao
Sep 3, 2013·Journal of Molecular Graphics & Modelling·Bruno L OliveiraJoão D G Correia

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.