Applying pattern recognition methods to analyze the molecular properties of a homologous series of nitrogen mustard agents

Abstract

The purpose of this research was to analyze the pharmacological properties of a homologous series of nitrogen mustard (N-mustard) agents formed after inserting 1 to 9 methylene groups (-CH 2 -) between 2 -N(CH 2 CH 2 Cl) 2 groups. These compounds were shown to have significant correlations and associations in their properties after analysis by pattern recognition methods including hierarchical classification, cluster analysis, nonmetric multi-dimensional scaling (MDS), detrended correspondence analysis, K-means cluster analysis, discriminant analysis, and self-organizing tree algorithm (SOTA) analysis. Detrended correspondence analysis showed a linear-like association of the 9 homologs, and hierarchical classification showed that each homolog had great similarity to at least one other member of the series-as did cluster analysis using paired-group distance measure. Nonmetric multi-dimensional scaling was able to discriminate homologs 2 and 3 (by number of methylene groups) from homologs 4, 5, and 6 as a group, and from homologs 7, 8, and 9 as a group. Discriminant analysis, K-means cluster analysis, and hierarchical classification distinguished the high molecular weight homologs from low molecular weight homologs. As the number of methylene groups increased the aqueous solubility decreased, dermal permeation coefficient increased, Log P increased, molar volume increased, parachor increased, and index of refraction decreased. Application of pattern recognition methods discerned useful interrelationships within the homologous series that will determine specific and beneficial clinical applications for each homolog and methods of administration.

A new paradigm for pattern recognition of drugs

“…It is possible to make a supposition about the binding mechanism of the described agents [e.g., 2,4,6]. However, the given approaches are usually used for the consideration of sets with a unique scaffold [e.g., 5,[8][9][10]. At the same time there is a problem of quantum correlation or quantum conformity for the various classes of compounds acting by similar mechanisms.…”

“…At the same time there is a problem of quantum correlation or quantum conformity for the various classes of compounds acting by similar mechanisms. Besides, most of the existing approaches to pattern recognition of drugs fail to account for the conformational state of the drugs, which determines the shape, size, and energy characteristics of a molecule and hence its potential ability to bind with a receptor [5,[8][9][10]. Therefore, the present study offers a new paradigm for pattern recognition of drugs taking into consideration these problems.…”

Bile-Acid-Appended Triazolyl Aryl Ketones: Design, Synthesis, In Vitro Anticancer Activity and Pharmacokinetics in Rats

“…In addition, adsorption, distribution, metabolism and excretion (ADME) properties and physiochemical properties of the synthesized analogs were calculated using molinspiration cheminformatics [ 45 , 46 ]. Additionally, percentage absorption and drug-likeness model score were also calculated using the reported formula [ 47 ] and Molsoft [ 48 ], respectively. As indicated by the TPSA values (between 60 and 160Å 2 ), all the analogs ( 6aa – df ) possessed better intestinal absorption ability over the blood–brain barrier (BBB) penetration power.…”

Homology Modeling and Blind Docking Approach Studies of Pig Heart Fumarase

“…Finally, the electronic effects of the ligands were taking up from the literature [11], whereas their partition coefficient and steric effects were calculated. The first was calculated online by using the molinspiration site (Molinspiration, Bratislava, Slovak Republic) [12]. Then, the steric effect was calculated by using the electrostatic potential as was reported by Suresh [13].…”