Prediction of biological activity profiles of cyanobacterial secondary metabolites

Over the past decade cyanobacteria have become an interesting source of new classes of pharmacologically active natural products. Some cyanobacterial secondary metabolites (CSMs) are also well known for their toxic effects on living species. The PASS (Prediction of Activity Spectra for Substances) computer program, which is able to simultaneously predict more than one thousand biological and toxicological activities from only the structural formulas of the chemicals, was used to predict the biological activity profile of 681 CSMs. Multivariate methods were employed to structure and analyse this wealth of biological and chemical information. PASS predictions were successfully compared to the available information on the pharmacological and toxicological activity of these compounds.     

Prediction of vibrational spectra from microwave spectra

Explicit and simple relations are derived for the Kivelson-Wilson parameters which can directly generate the vibrational spectrum of XY₂ bent type molecules. These relations are also shown to generate the above parameters for the different isotopes of a parent molecule. These predictions are verified in the case of some molecules of the above symmetry for which experimental microwave studies have been made.     

Computer-aided prediction of biological activity spectra for organic compounds: the possibilities and limitations

Russian Chemical Bulletin - We describe the current version of the PASS program for prediction of biological activity spectra of organic compounds based on analysis of structure—activity...     

Prediction of biological activity for high-throughput screening using binary kernel discrimination

High-throughput screening has made a significant impact on drug discovery, but there is an acknowledged need for quantitative methods to analyze screening results and predict the activity of further compounds. In this paper we introduce one such method, binary kernel discrimination, and investigate its performance on two datasets; the first is a set of 1650 monoamine oxidase inhibitors, and the second a set of 101 437 compounds from an in-house enzyme assay. We compare the performance of binary kernel discrimination with a simple procedure which we call "merged similarity search", and also with a feedforward neural network. Binary kernel discrimination is shown to perform robustly with varying quantities of training data and also in the presence of noisy data. We conclude by highlighting the importance of the judicious use of general pattern recognition techniques for compound selection.     

Prediction of olefin IR spectra reasoning from their mass spectra

Possible appliance of low resolution mass spectra in QSPR studies to predict IR spectra of olefins in gas phase is considered. The prediction quality is characterized by values of correlation coefficients from 0.961 to 1.00 between computed and experimental vector representations of IR spectra.     

Prediction of the vibrational spectra of interacting water molecules

A system of computer programs has been developed to predict and interpret the infrared spectra of molecules, ions, radicals and of chemically interacting species. The frequency parameters (or force constants) and the intensity parameters (or atomic polar tensors (APTs)) are calculated using the Gaussian-76 program for $\text{ab}$$\text{initio}$ quantum mechanical calculations with a 4–31G basis set. The resultant wavenumbers and intensities have been used to predict the fundamental infrared spectra of water molecules interacting with different molecular species. The corresponding wavenumber shifts and intensity changes from the spectrum of the non-interacting water molecule are dependent upon both the geometrical orientation and the electron-donating properties of the interacting species. The intensity parameters can be further analyzed by using the charge-charge flux-overlap (CCFO) interpretation of the APTs. This interpretation is helpful in pinpointing the exact source of the perturbation that produces the intensity change. The significance is discussed of each of these CCFO terms in predicting the infrared intensities of molecules undergoing intermolecular interaction.     

Robustness of biological activity spectra predicting by computer program PASS for noncongeneric sets of chemical compounds

The computer system PASS provides simultaneous prediction of several hundreds of biological activity types for any drug-like compound. The prediction is based on the analysis of structure-activity relationships of the training set including more than 30000 known biologically active compounds. In this paper we investigate the influence on the accuracy of predicting the types of activity with PASS by (a) reduction of the number of structures in the training set and (b) reduction of the number of known activities in the training set. The compounds from the MDDR database are used to create heterogeneous training and evaluation sets. We demonstrate that predictions are robust despite the exclusion of up to 60% of information.     

Photoacoustic spectra of some biological metal chelates

Photoacoustic spectra of Ni2+ in three new chelates containing azolo-2,4 pentanedione derivatives have been recorded and analysed in the visible region. The approximate symmetry of Ni2+ has been found to be octahedral. The d-d transitions in the red region show some similarity with those of nickel chloride and nickel acetate. In each case two charge-transfer bands appear in the violet region.     

13C NMR spectra and biological activity of N-(1H-benzimidazol-2-yl)benzamides

Derivatives of 1H-benzimidazol-2-amine and halo-, nitro-, methoxy-, and hydroxy-substituted benzoic acids were synthesized, and their fungicide activity against pure Fusarium culmorum and Helminthosporium sativum cultures and pathogenic microflora of wheat and barley seeds in laboratory and field tests was studied. Some compounds were found to exhibit a strong fungicide activity.     

Computer-aided prediction for medicinal chemistry via the Internet

Some computational tools for medicinal chemistry freely available on the Internet were compared to examine whether the results of prediction obtained with different methods coincided or not. It was shown that the correlation coefficients varied from 0.65 to 0.90 for log P (seven methods), from 0.01 to 0.73 for aqueous solubility (four methods), and from 0.19 to 0.73 for drug-likeness (three methods). While for log P estimates, reasonable average pairwise correlation was found, for aqueous solubility and drug-likeness it was rather poor. Therefore, using computational tools freely available via the Internet, medicinal chemists should evaluate their accuracy versus experimental data for particular series of compounds. In contrast to prediction of above mentioned properties, which can be done with several Internet tools, wide profiling of biological activity can be obtained only with PASS Inet (http://www.ibmc.msk.ru/PASS). PASS Inet was tested by a dozen medicinal chemists for compounds from different chemical series with various kinds of biological activity, and in the majority of cases the results of prediction coincided with the experiments. New anxiolytics, antiarrhythmics, antileishmanials, and other biologically active agents have been identified on this basis. The advantages and limitations of computer-aided predictions for medicinal chemistry via the Internet are discussed.     

Computer-aided prediction for medicinal chemistry via the Internet1

Some computational tools for medicinal chemistry freely available on the Internet were compared to examine whether the results of prediction obtained with different methods coincided or not. It was shown that the correlation coefficients varied from 0.65 to 0.90 for log P (seven methods), from 0.01 to 0.73 for aqueous solubility (four methods), and from 0.19 to 0.73 for drug-likeness (three methods). While for log P estimates, reasonable average pairwise correlation was found, for aqueous solubility and drug-likeness it was rather poor. Therefore, using computational tools freely available via the Internet, medicinal chemists should evaluate their accuracy versus experimental data for particular series of compounds. In contrast to prediction of above mentioned properties, which can be done with several Internet tools, wide profiling of biological activity can be obtained only with PASS Inet (http://www.ibmc.msk.ru/PASS). PASS Inet was tested by a dozen medicinal chemists for compounds from different chemical series with various kinds of biological activity, and in the majority of cases the results of prediction coincided with the experiments. New anxiolytics, antiarrhythmics, antileishmanials, and other biologically active agents have been identified on this basis. The advantages and limitations of computer-aided predictions for medicinal chemistry via the Internet are discussed.     

Studies on the biological activity of tocotrienols

Tocotrienols were evaluated for activity against transplantable murine tumors inoculated i.p. into mouse, and the activities of two tocotrienols and alpha-tocopherols were compared. When the compounds were injected i.p., alpha- and gamma-tocotrienols were effective against sarcoma 180, Ehrlich carcinoma, and IMC carcinoma, and gamma-tocotrienol showed a slight life-prolonging effect in mice with Meth A fibrosarcoma, but the tocotrienols had no antitumor activity against P388 leukemia at doses of 5-40 mg/kg/d. On the other hand alpha-tocopherol had only a slight effect against sarcoma 180 and IMC carcinoma. The antitumor activity of gamma-tocotrienol was higher than that of alpha-tocotrienol. Tocotrienols showed growth inhibition of human and mouse tumor cells when the cells were exposed to these agents for 72 h in vitro, whereas tocopherol did not show any marked cytotoxic activity. Alpha- and gamma-tocotrienols had inhibitory effects on lipid peroxidation of murine microsomes by adriamycin.     

Computer aided prediction of biological activity spectra: evaluating versus known and predicting of new activities for thiazole derivatives

Computer aided prediction of biological activity spectra by the computer program PASS was applied to a set of 89 new thiazole derivatives. Experimentally tested activities (NSAID, local anaesthetic and antioxidant) coincide with the experiment in 70.8% cases, that exceeds significantly the random guess-work (approximately 0.1%). Therefore, computer aided prediction using the Prediction of Activity Spectra for Substances (PASS) system (http://www.ibmh.msk.su/PASS) provides a reliable basis for planning of synthesis and experimental study for new compounds. New psychotropic activities are predicted for some compounds from the series under study. In particular, 7, 44 and 55 compounds likely have anxiolytic, anticonvulsant and cognition enhancer effects, respectively. Most of these compounds have the estimated values of probability to be active (Pa) less than 60%. Therefore, if their activity will be confirmed by the experiment, they might occur to be New Chemical Entities.     

Computer aided prediction of biological activity spectra: Evaluating versus known and predicting of new activities for thiazole derivatives

Computer aided prediction of biological activity spectra by the computer program PASS was applied to a set of 89 new thiazole derivatives. Experimentally tested activities (NSAID, local anaesthetic and antioxidant) coincide with the experiment in 70.8% cases, that exceeds significantly the random guess-work (～0.1%). Therefore, computer aided prediction using the Prediction of Activity Spectra for Substances (PASS) system (http://www.ibmh.msk.su/PASS) provides a reliable basis for planning of synthesis and experimental study for new compounds. New psychotropic activities are predicted for some compounds from the series under study. In particular, 7, 44 and 55 compounds likely have anxiolytic, anticonvulsant and cognition enhancer effects, respectively. Most of these compounds have the estimated values of probability to be active ( P a ) less than 60%. Therefore, if their activity will be confirmed by the experiment, they might occur to be New Chemical Entities.     

Simulated photoelectron spectra of the cyanide-water anion via quasiclassical molecular dynamics

We present the simulated photoelectron spectrum (PES) for cyanide-water CN(H(2)O)(-) based on quasiclassical trajectory molecular dynamics (QCT-MD). Using density functional theory to generate trajectories and to calculate vertical detachment energies, we obtain simulated spectra that are in qualitative agreement with experiment. We obtain a theoretical 12 → 300 K temperature red shift of 0.1 eV as compared to an experimental redshift of 0.25 eV. The calculated linewidths of 0.3 eV are in excellent agreement with experiment. Our trajectories show that the temperature red shift as being dominated by dynamics within the basin of the N-bound minimum, however, at 300 K we predict conversion into the basin of the C-bound minimum, equilibrating at a 80:20 ratio of N- vs C-bound mixture. We discuss the potential advantages of QCT-MD over anharmonic Franck-Condon analysis such as natural incorporation of anharmonicity (as necessary for weakly bound systems), and reduced computational scaling, but also drawbacks such as neglect of final-state (e.g., Duschinsky) effects.     

Studies on the biological activity of some nitrothiophenes

The biological activity of nineteen substituted thiophenes (3) have been assessed by evaluating the minimum inhibitory concentration required to inhibit the growth of E. coli, M. luteus and A. niger. The series displays a wide range of activities with 2-chloro-3,5-dinitrothiophene (3a) or 2-bromo-3,5-dinitrothiophene (3c) showing the highest activity against all three organisms, while the simplest compound of the series, 2-nitrothiophene (3s) shows the smallest activity in each case. The mode of action of 3a and 3c is thought to involve nucleophilic attack by intracellular thiols at the 2-position of the heterocyclic ring leading to displacement of halogen, but other active derivatives, such as 2,4-dinitrothiophene (3h) and 5-nitrothiophene-2-carbaldehyde (3d) which have no displaceable halogen or leaving group are thought to act by forming Meisenheimer complexes.     

Relevance of the electric-dipole--electric-quadrupole contribution to Raman optical activity spectra

We examine the importance of the electric-dipole--electric-quadrupole polarizability tensor in the intensity theory of Raman optical activity (ROA) spectra. Using density functional theory, ROA spectra of organic cyclic compounds, alanine, oligoalanines, and examples from the literature are analyzed in detail, and a statistical investigation is performed. It is found that the contribution of the electric-dipole--electric-quadrupole tensor is often small, except for some special cases that involve C-H stretching vibrations.