Criteria for the comparison of chemical structures and principles of construction of an information language for a logical information system for biologically active compounds

Avidon, V. V.

doi:10.1007/bf00757886

Cited by 6 publications

(7 citation statements)

References 2 publications

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“…This approach was initiated in the beginning of the 1970s in the framework of the State System for Registration of New Chemical Compounds Synthesized in the USSR . As far as we are aware of, PASS currently has no direct equivalent in terms of its breadth of predicted activity spectrum.…”

Section: Introductionmentioning

confidence: 99%

PASS Biological Activity Spectrum Predictions in the Enhanced Open NCI Database Browser

Poroikov

Филимонов

Ihlenfeldt

et al. 2002

J. Chem. Inf. Comput. Sci.

220

148

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The application of the program PASS (Prediction of Activity Spectra for Substances) to about 250 000 compounds of the NCI Open Database and the incorporation of over 64 million PASS predictions in the Enhanced NCI Database Browser are described. A total of 565 different types of activity are included, encompassing general pharmacological effects, specific mechanisms of action, known toxicities, and others. Application of this Web-based service to prediction of activities of the kinds "Angiogenesis inhibitor," "Antiviral (HIV)", and a set of activities that can be associated with antineoplastic action are reported. For this latter data set, a very substantial enrichment over random selection was found in the PASS predictions. It is shown how the user can conduct complex searches by combining ranges of PASS-predicted probabilities of compounds to be active or to be inactive, respectively, with, e.g., value ranges of physicochemical parameters, presence or absence of particular substructural fragment, and other search criteria.

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Section: Introductionmentioning

confidence: 99%

PASS Biological Activity Spectrum Predictions in the Enhanced Open NCI Database Browser

Poroikov

Филимонов

Ihlenfeldt

et al. 2002

J. Chem. Inf. Comput. Sci.

220

148

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“…Computation of fragmental descriptors does not require the knowledge of the geometry and electronic structure of molecules; structural fragments are more easily interpretable than topological indices. Molecular fragments are successfully used in diversity analysis of large databases , and in structure−property studies. − The recently developed PASS method, , used for estimation of a wide spectrum of biological activities, is also based on molecular fragments (augmented atoms). The success of the fragmental approach in QSAR/QSPR studies depends on the diversity of structural fragments as well as on the flexibility of atomic classification.…”

Section: Introductionmentioning

confidence: 99%

“…Molecular fragments are successfully used in diversity analysis of large databases 36,37 and in structure-property studies. [38][39][40][41][42][43] The recently developed PASS method, 39,44 used for estimation of a wide spectrum of biological activities, is also based on molecular fragments (augmented atoms). The success of the fragmental approach in QSAR/QSPR studies depends on the diversity of structural fragments as well as on the flexibility of atomic classification.…”

Section: Introductionmentioning

confidence: 99%

Anti-HIV Activity of HEPT, TIBO, and Cyclic Urea Derivatives: Structure−Property Studies, Focused Combinatorial Library Generation, and Hits Selection Using Substructural Molecular Fragments Method

Solov'ev

Varnek

2003

J. Chem. Inf. Comput. Sci.

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Substructural molecular fragments (SMF) method [Solov'ev, V. P.; Varnek, A.; Wipff, G. J. Chem. Inf. Comput. Sci. 2000, 40, 847-858] was applied to assess anti-HIV activity for large data sets for three families of compounds: 1-[2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) derivatives, tetrahydroimidazobenzodiazepinone (TIBO) derivatives, and cyclic urea (CU) derivatives. The SMF method uses 49 types of topological descriptors (atom/bond sequences and "augmented atoms") which, being coupled with 3 linear and nonlinear fitting equations, allows the user to generate up to 147 structure-property models. For each family of compounds, the modeling was performed on several training sets followed by the validation calculations where three best fit models were applied. Calculated activities well reproduce available experimental data. On the basis of the "optimal" molecular fragments, the focused combinatorial library containing 252 virtual HEPT derivatives has been generated. Its filtering led to several hits potentially possessing anti-HIV activity.

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“…The first attempts to develop computer-aided methods for the prediction of biological activity from chemical structures were made in the 1970s [14,15]. Further progress was made in the following decade [16][17][18][19], but for various reasons the problem was not completely solved at that time.…”

Section: Pass Approachmentioning

confidence: 99%

Multi-Targeted Natural Products Evaluation Based on Biological Activity Prediction with PASS

Lagunin

Филимонов²,

Poroikov³

2010

CPD

134

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Natural products found a wide use in folk medicine. Presently, when routine development of new drugs faced a considerable challenge, they become an inspiration and valuable source in drugs discovery. Rather complex and diverse chemical structures of natural compounds provide a basis for modulation of different biological targets. Natural compounds exhibit a multitargeted action that may lead to additive/synergistic or antagonistic effects. Rational design of more safe and potent pharmaceuticals requires an estimation of probable multiple actions of natural products. Our software PASS can perform such estimation. It predicts with reasonable accuracy over 3500 pharmacotherapeutic effects, mechanisms of action, interaction with the metabolic system, and specific toxicity for drug-like molecules on the basis of their structural formulae. We analyzed PASS predictions utilizing PharmaExpert, which performs selection of compounds with multiple mechanisms of action, analysis of activity-activity relationships and drug-drug interactions. The paper describes an application of PASS and PharmaExpert to the evaluation of biological activity of natural compounds including marine sponge alkaloids, triterpenoids of lupane group, and their derivatives. Proposed computer-aided methods can generate combinatorial libraries of macrolides. They help to select the most promising pharmaceutical leads with the required properties. Case study, based on the analysis of biological activity spectra predicted for St John's Wort constituents, clearly demonstrates capabilities of computational methods in the evaluation of multitargeted actions, additive/synergistic and/or antagonistic effects of natural products.

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Criteria for the comparison of chemical structures and principles of construction of an information language for a logical information system for biologically active compounds

Cited by 6 publications

References 2 publications

PASS Biological Activity Spectrum Predictions in the Enhanced Open NCI Database Browser

PASS Biological Activity Spectrum Predictions in the Enhanced Open NCI Database Browser

Anti-HIV Activity of HEPT, TIBO, and Cyclic Urea Derivatives: Structure−Property Studies, Focused Combinatorial Library Generation, and Hits Selection Using Substructural Molecular Fragments Method

Multi-Targeted Natural Products Evaluation Based on Biological Activity Prediction with PASS

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