8/12/2019 Regression Analysis 4

1/2

Regression Analysis (RA)The application of the biochromatographicdata in QSAR analysis of some thiazole derivativeswith H-antihistamine activity was described in theprevious papers (!"# Additionally$ the lipophilicitydata ofsolutes were applied as independent variablesin the regression analysis# %n the basis ofdescribedresults it wasfound that log & is a crucialindicatorof the H'-antihistamine effect of thiazolederivatives# An increase in thelog & value favorshigher biological activity of the tested compounds#umerous significant multivariate

relationships ofthe antihistamine effect involved log & values ()!"#The present RA started withintercorrelation studyof the used independent variables# %nly the uncorrelatedphysicochemical data can beused in the multivariaterelationships (see Table !"# e*t$ the systematic analysis was performed#As result$over +, statistically significant relationshipswere determined# The obtained relationshipsofH-antihistamineeffect and molecular descriptorsvalues e*plained ).!/ of the variance# The bestunivariate and multivariaterelationships are shownin Table 0#1t is evident in QSAR investigation that thebest correlations obtained by theRA method for thiazolederivatives 1-19withH'-antihistamine activity underline important role of hydrophobicand steric parameters for this 2ind of activity# The same parameters (A 34 54 log &4 log 64 7R4 a" with strong

factor loadings built the most significant factor$ which was obtained in factor analysis of the investigated

compounds 1-19('"# 1t is also evident that some of the electronic parameters are very important# Theseparameters were lin2ed to higher and lower compounds activity via 68A (a$ A9$ HeH%7%$ QAr3" and &:A (a$ log

&$ Hh$H%7%$ Q" methods#

All calculated significant relationships can be applied to predict the pharmacological activity of new drug

candidates# The best of these relationships can be e*pressed by the e;uation 20 (Table 0"$ which e*plains .!/

of the total variance ,#,0" log & ? ,#'@@(>,#,0" m ) ,#'(> ,#,!" QArArh$

1t was concluded that the high lipophilicity and dipole moment combined with less negative charge on aromatic

nitrogen atom are the properties of active H-antihistamine thiazole derivatives# 1t is clearly seen that e;uation

20 may havepredictive value for the design of new thiazole derivatives as the H -antihistamine drugs (Table

and 8ig# @"# The correlation of calculated pA'"values of the tested compounds predicted by the useof the abovementioned e;uation versus theirpA(H" values obtained from biological tests wassignificant (R'= ,#.!"#However$ the range of pAdata of the e*aminedcompounds obtained from biological tests clusteredaround twosets (compounds 1-11 have pAvaluesbetween #,, and !#,4 compounds 12-19 have pAvalues between !#+and 0#@+"# 8or the two-point datadistribution the possibility of coincidence in themodel presented in the figurecannot be eliminated#

CONCLUSIONThe dimensionality of physicochemical parameters was reduced by the &:A and 68A methods$

And the subset of variables more effective for classification the thiazole derivatives according to their degree of

anti-H activity were determined# The &:A method can be useful as an efficient tool for initial selection of the

parameters which significantly enhance anti-H'activity# The analysis determined the direction of the lead

compounds modification# The results of 68A method showed that $ A9$ B'$Hh$ eH%7%and Q parameters are 2ey

properties for e*plaining the HAr-antihistamine activity of thiazole derivatives 1-19but log & is also importantfor design of new thiazoles e*hibiting antihistamine activity# The determined discrimination function for groups

A and 9 can be an efficient tool in further investigations# Cood univariate and multivariate relationships

obtained by the use of RA method can be used for predicting the ;uantitative effect of H 'antihistamine activity

of different thiazole derivatives# These relationships involved the parameters determined via68A and &:Amethods#

Analisis Regresi ( RA )

Penerapan data biochromatographic dalam analisis QSAR beberapa turunan tiazoldengan aktivitas H1 - antihistamin digambarkan pada paper sebelumna ( !-" ) # Selain itu $data lipophilicit zat terlarut ang diterapkan digunakan sebagai variabel independen dalamanalisis regresi # Atas dasar hasil ang ditemukan bah%a log P merupakan indikator pentingdari e&ek H1 - antihistamin dari derivati& thiazole # Peningkatan nilai log P akan menokongaktivitas biologis ang lebih tinggi dari sena%a ang diu'i # anak hubungan multivariatang signi&ikan dari e&ek antihistamin melibatkan nilai log P ( !-" ) # Pemaparan RA dimulai

8/12/2019 Regression Analysis 4

2/2