ABSTRACT
The review discusses main approaches to searching for new low-molecular-weight inhibitors of coagulation factors IIa, Xa, IXa, and XIa and the results of such studies conducted from 2015 to 2018. For each of these factors, several inhibitors with IC50 < 10 nM have been found, some of which are now tested in clinical trials. However, none of the identified inhibitors meets the requirements for an "ideal" anticoagulant, so further studies are required.
Subject(s)
Anticoagulants/pharmacology , Blood Coagulation Factors/antagonists & inhibitors , Computer-Aided Design , Anticoagulants/chemistry , Blood Coagulation Factors/metabolism , Humans , Molecular WeightABSTRACT
We calculated 219 topological, electronic, and steric indices for each of 59 studied embryotoxic benzylalkylamines and indolamines. Statistically significant equations correlating embryotoxicity and five calculated parameters were obtained using the method of step multiple regression. The prognostic power of the equation was 88-90%. Discriminant functions obtained by step discriminant analysis allowed prediction of the superactivity of benzylalkylamines and indolamines with 83-87% probability.
Subject(s)
Biogenic Amines/toxicity , Embryo, Nonmammalian/drug effects , Animals , Discriminant Analysis , Prognosis , Regression Analysis , Sea Urchins/drug effects , Sea Urchins/embryology , Software , Structure-Activity RelationshipABSTRACT
Discriminant functions were obtained on the basis of experimental data on the superactivity of synthetic analogues of the natural biogenic amines (26 active and 33 superactive derivatives of benzene and indole), which allow prognostication of the superactivity of embryotoxic compounds with respect to sea urchin embryos on the basis of calculated parameters of the molecules. During reclassification of molecules of the learning sample, the percentage of correct recognition is 73.1 for active, 87.9 for superactive, and 81.4% for the entire data bank. The prognostication capacity of the obtained functions is 73-80%.
Subject(s)
Biogenic Amines/toxicity , Computer Simulation , Embryo, Nonmammalian/drug effects , Models, Biological , Animals , Discriminant Analysis , Prognosis , Sea Urchins , Structure-Activity RelationshipABSTRACT
The shortcomings of available approaches to determination of the character of chemical compounds biological activity according to calculated, tabular and experimental parameters have been analyzed using statistic methods. Some ways of available algorithms improving are given.
Subject(s)
Psychotropic Drugs/pharmacology , Algorithms , Animals , Discriminant Analysis , Methods , PrognosisSubject(s)
Leukemia, Lymphoid/diagnosis , Leukemia, Myeloid, Acute/diagnosis , Adolescent , Child , Child, Preschool , Humans , Leukemia, Lymphoid/drug therapy , Leukemia, Myeloid, Acute/drug therapy , Prognosis , Regression, Psychology , Remission, Spontaneous , Retrospective Studies , Time FactorsABSTRACT
Antibacterial activity of 2 natural and 12 semisynthetic penicillins against 5 strains of grampositive bacteria was determined and quantum chemical estimation of their molecules was performed with the Hukkel method. The data were indicative of the fact that antibacterial activity of the penicillins was connected with the acceptor properties of their molecules.
