An in silico 3D pharmacophore model of chalcones useful in the design of novel antimalarial agents.

An in silico 3D pharmacophore model of chalcones useful in the design of novel antimalarial agents. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

An in silico 3D pharmacophore model of chalcones useful in the design of novel antimalarial agents. Abstract Text:

Malaria, the most important of the human parasitic diseases, causes about 500 million infections worldwide and over 1 million deaths every year. The search for novel drug candidates against specific parasitic targets is an important goal for antimalarial drug discovery. Recently the antimalarial activity of chalcones has generated great interest. These compounds are small non-chiral molecules with relative high lipophilicity (clogP approximately 5-7), have molecular weights in the range of 300 to 600 g/mol, and possess in vivo efficacy against both P. berghei and P. yeolii. Preliminary data on our on-going chalcone synthesis project indicate that these compounds are active in vitro against P. falciparum, but are rapidly metabolized in liver microsome assays. Structurally-related compounds not including the enone linker are found to be much more metabolically stable and yet have comparable in vitro efficacy. In this study, we have utilized the efficacy data from an in-house on-going chalcone project to develop a 3D pharmacophore for antimalarial activity and used it to conduct virtual screening (in silico search) of a chemical library which resulted in identification of several potent chalcone-like antimalarials. The pharmacophore is found to contain an aromatic and an aliphatic hydrophobic site, one hydrogen bond donor site, and a ring aromatic feature distributed over a 3D space. The identified compounds were not only found to be potent in vitro against several drug resistant and susceptible strains of P. falciparum and have better metabolic stability, but included one with good in vivo efficacy in a mouse model of malaria.

An in silico 3D pharmacophore model of chalcones useful in the design of novel antimalarial agents. Publishing Authors By Initials

For similar biochemical phenomena, metabolism, and nutrition: biochemical phenomena: structure-activity relationship research abstracts see: biochemical phenomena, metabolism, and nutrition: biochemical phenomena: structure-activity relationship research

PUBMED ID PMID:

MEDLINE DATE:

An in silico 3D pharmacophore model of chalcones useful in the design of novel antimalarial agents. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Medicinal chemistry (Sh?riqah (United Arab Emirate

VOLUME: 3

Page Numbers: 317-26

Journal Abbreviation:

ISSN: 1573-4064

DAY: 26

MONTH: Jul

YEAR: 2007

An in silico 3D pharmacophore model of chalcones useful in the design of novel antimalarial agents. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 101240303

An in silico 3D pharmacophore model of chalcones useful in the design of novel antimalarial agents. Keywords Mesh Terms:

KEYWORDS: Structure-Activity Relationship

MESH TERMS: drug effects

Chemical & Substance for Abstract: An in silico 3D pharmacophore model of chalcones useful in the design of novel antimalarial agents. Information

Substance Name: Chalcones

Registry Number: 0

Grant and Affiliation Information for An in silico 3D pharmacophore model of chalcones useful in the design of novel antimalarial agents.

AFFILIATION: Department of Medicinal Chemistry, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. apurba.bhattacharjee@na.amedd.army.mil

Country: Netherlands

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: Med Chem

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

An in silico 3D pharmacophore model of chalcones useful in the design of novel antimalarial agents Related Publications

• An in silico 3D pharmacophore model of chalcones useful in the design of novel antimalarial agents.
• An in vitro investigation into the effects of retained coronal dentine on the strength of a tooth restored with a cemented post and partial core restoration.
• An in vitro study of coronal microleakage in root-canal-treated teeth restored by the post and core technique.
• Blood-transfusion around the world.
• Fenestration.
• Iron and oxygen: a biologically damaging mixture.
• Monitoring clinical quality in rare disease services--experience in England.
• Plasma hypoxanthine levels in ARDS: implications for oxidative stress, morbidity, and mortality.
• The importance of cold and warm cardiac ischemia for survival after heart transplantation.
• The influence of red meat intake upon the response to a resistance exercise-training program in older Australians.
• Written information for patients.