Design of New Cognition Enhancers:  From Computer Prediction to Synthesis and Biological Evaluation

Geronikaki, Athina; Dearden, John C.; Филимонов, Д. А.; Galaeva, I. P.; Garibova, Taissia L.; Gloriozova, Tatyana A.; Krajneva, Valentina; Lagunin, Alexey; Macaev, Fliur; Molodavkin, Guenadij; Poroikov, Vladimir; Pogrebnoi, Serghei; Shepeli, Felix; Воронина, Т. А.; Tsitlakidou, Maria; Vlad, L.

doi:10.1021/jm031086k

Cited by 71 publications

(39 citation statements)

References 27 publications

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“…A) (Geronikaki et al [6]). The substituted thiazol-2-ylamine (5 mmol), a slight excess of the aldehyde (6 mmol) and a few drops of piperidine, in ethanolic solution (15 mL), were refluxed in a water bath for 3 h. After cooling, the final products were precipitated, filtered, and recrystallized.…”

Section: Chemical Synthesis: General Methods For Preparation Of Schiffmentioning

confidence: 99%

“…Experiments were performed according to the method described in our previous paper [6]. The equipment comprised two adjacent chambers, one light and one dark.…”

Section: Biological Assaymentioning

confidence: 99%

“…We recently published a study of a number of such compounds with cognition-enhancing ability [6]. We used the PASS software [7 -10] to predict cognition enhancing properties of a wide range of compounds, and the DEREK software [11,12] to predict potential carcinogenicity, mutagenicity and skin-sensitization of the compounds, to avoid having to synthesize and test any with significant toxicity.…”

Section: Introductionmentioning

confidence: 99%

“…In the study referred to [6], a total of 5494 compounds was designed and subjected to PASS prediction of cognition-enhancing activity. From the PASS results, eight compounds were selected.…”

Section: Introductionmentioning

confidence: 99%

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QSAR Investigation of New Cognition Enhancers

Dearden¹,

Hewitt²,

Geronikaki³

et al. 2009

QSAR Comb. Sci.

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Increasing longevity means that there is an increased likelihood of loss of cognitive functions and of incidence of dementias. There is thus a greater demand for cognitionenhancing (noçtropic) drugs. Some such drugs are already available, but many display serious side-effects. We have designed, synthesized and tested a number of novel chemical entities that are predicted by the PASS software to be potential noçtropic agents. The results have been subjected to QSAR (quantitative structure -activity relationship) analysis, and good QSAR correlations, with external validation, have been obtained, which can be used predictively to guide design of additional potential cognitionenhancers.

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Section: Chemical Synthesis: General Methods For Preparation Of Schiffmentioning

confidence: 99%

“…Experiments were performed according to the method described in our previous paper [6]. The equipment comprised two adjacent chambers, one light and one dark.…”

Section: Biological Assaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

QSAR Investigation of New Cognition Enhancers

Dearden¹,

Hewitt²,

Geronikaki³

et al. 2009

QSAR Comb. Sci.

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show abstract

“…In this case, the P a values can be interpreted as P a [0.7, 0.5 \ P a \ 0.7 and P a \0.5. As a result, the possibility of finding this activity in the experiments will be high, less and least, respectively [15].…”

Section: Introductionmentioning

confidence: 99%

Green synthesis of polyhydroquinolines via MCR using Fe3O4/SiO2-OSO3H nanostructure catalyst and prediction of their pharmacological and biological activities by PASS

2017

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In this work, a library of diverse chemically and medicinally important heterocyclic polyhydroquinoline derivatives was efficiently prepared via a one-pot multicomponent reaction starting from various raw materials including aromatic aldehydes, dimedone or 1,3-cyclohexandione, ethyl acetoacetate or methyl acetoacetate and ammonium acetate in the presence of Fe 3 O 4 /SiO 2 -OSO 3 H as a sulfonated silica-based magnetic nanocatalyst in high yields. Main advantages of the present practical approach are ready availability of starting materials, non-toxicity, inexpensiveness, ease of workup procedure, diversity orientation synthesis and an eco-friendly nature of the reaction. The nanocatalyst was characterized by Fourier transform infrared (FT-IR) spectra, scanning electron microscopy (SEM) images and energy-dispersive X-ray spectroscopy (EDX) spectra. The nanocatalyst was simply recovered using an external magnet and reused several times. Then, the pharmacological and biological activities of the products were theoretically examined by the prediction of activity spectra for substances (PASS) program.

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Knowledge‐Based and Computational Approaches to In Vitro Safety Pharmacology

Scheiber

Bender

Azzaoui

et al. 2009

Hit and Lead Profiling

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Legitimate estimates suggest that developing a novel chemical entity (NCE) as a drug can cost up to U.S.$ 2 billion [1,2]. Still, about 10% of NCEs show serious adverse drug reactions (ADR) after market launch [3]. The majority of these ADRs can be avoided if possible undesired off-target effects of the compound are understood very early during the drug discovery process, that is, before clinical trials are started.This contribution focuses on computational methods that are used to assist and to guide in vitro preclinical safety pharmacology (PSP), a technology commonly applied in the pharmaceutical industry to evaluate compound selectivity profiles [4][5][6][7][8]. To develop compounds highly selective for a therapeutically relevant target and to avoid side effects or adverse drug reactions are key goals for every small-molecule drug discovery project. To achieve this, preclinical safety pharmacology approaches are commonly employed to screen compounds routinely in comparatively inexpensive, yet predictive assays to generate knowledge about possible polypharmacology. Thereby a comprehensive identification of possible liabilities can be achieved.We outline the currently available environment and approaches that can be applied for thorough computational analyses of in vitro safety pharmacology data. After discussing desirable and necessary prerequisites for the data input from a computational perspective, we address how this data is used to predict a general promiscuity score for a single compound. This approach aims to answer the general question of whether a compound will hit many targets or will be selective. Finally, we demonstrate how to computationally reveal possible single-target liabilities. This has the objective of understanding why a certain compound is active against a defined undesired target on a molecular level.The above approaches are collectively used to triage compounds prior to being screened in an in vitro safety pharmacology panel in order to prioritize compounds for testing and identify those which have the highest likelihood of being selective.Hit and Lead Profiling. Edited by Bernard Faller and Laszlo Urban

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Design of New Cognition Enhancers: From Computer Prediction to Synthesis and Biological Evaluation

Cited by 71 publications

References 27 publications

QSAR Investigation of New Cognition Enhancers

QSAR Investigation of New Cognition Enhancers

Green synthesis of polyhydroquinolines via MCR using Fe3O4/SiO2-OSO3H nanostructure catalyst and prediction of their pharmacological and biological activities by PASS

Knowledge‐Based and Computational Approaches to In Vitro Safety Pharmacology

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