Abstract
Quantitative structure–activity relationship study using artificial neural network (ANN) methodology were conducted to predict the inhibition constants of 127 symmetrical and unsymmetrical cyclic urea and cyclic cyanoguanidine derivatives containing different substituent groups such as: benzyl, isopropyl, 4-hydroxybenzyl, ketone, oxime, pyrazole, imidazole, triazole and having anti-HIV-1 protease activities. The results obtained by artificial neural network give advanced regression models with good prediction ability. The two optimal artificial neural network models obtained have coefficients of determination of 0.746 and 0.756. The lowest prediction’s root mean square error obtained is 0.607. Artificial neural networks provide improved models for heterogeneous data sets without splitting them into families. Both the external and cross-validation methods are used to validate the performances of the resulting models. Randomization test is employed to check the suitability of the models.
Highlights
Human immunodeficiency virus (HIV)-1 protease (HIV-1 PR) is an enzyme that belongs to the family of aspartic acid protease
Not surprising that protease enzyme represents the most attractive target site for development of therapeutic agents for treatment of acquired immunodeficiency syndrome (AIDS), the most agents target this site are cyclic urea and non-peptide cyclic cyanoquanidine derivatives. These agents contains many functional groups that interact with the wild type HIV-1 PR and its mutants, this interaction results in a complex of HIV-1 PR with the peptidomimetic inhibitors that produce an inactive HIV-1 PR and so inactive HIV [1,2,3,4,5]
This study aims to predict the anti-HIV-1 protease activity of the heterogeneous data set in reference [18] as one group without splitting them into categorizes
Summary
HIV-1 protease (HIV-1 PR) is an enzyme that belongs to the family of aspartic acid protease. Not surprising that protease enzyme represents the most attractive target site for development of therapeutic agents for treatment of AIDS, the most agents target this site are cyclic urea and non-peptide cyclic cyanoquanidine derivatives. These agents contains many functional groups that interact with the wild type HIV-1 PR and its mutants, this interaction results in a complex of HIV-1 PR with the peptidomimetic inhibitors that produce an inactive HIV-1 PR and so inactive HIV [1,2,3,4,5]
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