Biomaterial Database

Structure activity relationship of organic nitrates: an exploratory hypothesis via molecular models. 1992

T B Tzeng, and H L Fung

Department of Pharmaceutics, School of Pharmacy, State University of New York, Buffalo, Amherst 14260.

An exploratory attempt to explain the structure/activity relationship of organic nitrates was initiated. In addition to the partition coefficient, a new empirical parameter, F(5.8A), was used in this correlation. This new parameter denotes the number of times that two oxygen atoms in the molecule can be arranged at a distance of 5.8A. Vasodilating potencies (EC50s) and partition coefficients of 11 organic nitrates were obtained from a literature report, while their corresponding F(5.8A) values were obtained from manual determination using two molecular models, viz: CPK and Drieding. Via linear regression comparisons, we showed that F(5.8A) was a better physicochemical parameter than the partition coefficient in explaining the differences in the observed pharmacologic activity. When the two parameters were combined, greater than 90% of the variability of the potency was accounted for. These results suggest that the pertinent protein (most likely the activating enzyme) for organic nitrate activity may contain at least two 'oxygen-philic' attachment sites which are separated by a distance of 5.8A.

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
D009566	Nitrates	Inorganic or organic salts and esters of nitric acid. These compounds contain the NO3- radical.	Nitrate
D011506	Proteins	Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.	Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
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
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D014664	Vasodilation	The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE.	Vasodilatation,Vasorelaxation,Vascular Endothelium-Dependent Relaxation,Endothelium-Dependent Relaxation, Vascular,Relaxation, Vascular Endothelium-Dependent,Vascular Endothelium Dependent Relaxation
D066298	In Vitro Techniques	Methods to study reactions or processes taking place in an artificial environment outside the living organism.	In Vitro Test,In Vitro Testing,In Vitro Tests,In Vitro as Topic,In Vitro,In Vitro Technique,In Vitro Testings,Technique, In Vitro,Techniques, In Vitro,Test, In Vitro,Testing, In Vitro,Testings, In Vitro,Tests, In Vitro,Vitro Testing, In