title: Applying pattern recognition methods and structure property correlations to determine drug carrier potential of nicotinic acid and analogize to dihydropyridine.
abstract: Multivariate methods are utilized to compare nicotinic acid and dihydropyridine as a drug carrier. Nicotinic acid and dihydropyridine form ester groups on 10 beta-lactam antibiotics with an oxymethyl group forming a linkage between the antibiotic and the drug carrier (nicotinic acid or dihydropyridine). Calculated molecular properties are analyzed by self-organizing tree algorithm (SOTA), bivariate regression, cluster analysis, factor analysis, discriminant analysis, hierarchical classification, and principal coordinates analysis. Ten important pharmacological properties for each of the nicotinic acid and dihydropyridine antibiotic derivatives are numerically similar and highly correlated. Calculated molecular properties include molar refractivity, molar volume, parachor, index of refraction, partition coefficient (log P), polarizability, and polar surface area. Dermal permeability coefficients (Kp) for nicotinic acid derivatives are similar to values for dihydropyridine derivatives. Dermal permeabliity coefficients analyzed by hierarchical classification and SOTA analysis were shown to be closely interrelated and highly correlated. Ten properties of the nicotinic acid and dihydropyridine were compared by Passing-Bablok regression analysis and shown to be highly correlated (r=0.9879). Box plot analysis of 10 properties, inclusive of both groups of derivatives, showed narrow ranges in values. Cluster analysis of derivative properties showed the nicotinic acid derivatives to be highly similar to the dihydropyridine derivatives of the same antibiotics. Cluster analysis was performed by single linkage, complete linkage, and centroid linkage. Factor analysis showed the nicotinic acid derivatives to be interrelated and similar to the dihydropyridine derivatives. Discriminant analysis performed on all derivatives formed a single highly cohesive and non-differentiated cluster, demonstrating strong similarity among nicotinic acid and dihydropyridine derivatives. Principal coordinates analysis (determines similarity) of Kp values showed high similarity between the nicotinic acid and dihydropyridine antibiotic derivatives.
authors.affiliation: Medicinal Chemistry Laboratory, Chemistry Department, Durham Science Center, University of Nebraska, Omaha, NE 68182, USA. bartzatt@mail.unomaha.edu
authors.forename: Ronald
authors.initials: R
authors.lastname: Bartzatt
mesh_terms: D004095:Dihydropyridines / Q000032:analysis / Q000737:chemistry*; D004337:Drug Carriers / Q000032:analysis / Q000737:chemistry*; D009539:Nicotinic Acids / Q000032:analysis / Q000737:chemistry*; D010363:Pattern Recognition, Automated / Q000379:methods*; D013329:Structure-Activity Relationship
chemical_list: D004095:Dihydropyridines; D004337:Drug Carriers; D009539:Nicotinic Acids; C038806:1,4-dihydropyridine