Computer Aided Predicting the Biological Activity Spectra and Experimental Testing of New Thiazole Derivatives

Geronikaki, Athina; Poroikov, Vladimir; Hadjipavlou‐Litina, Dimitra; Филимонов, Дмитрий Алексеевич; Lagunin, Alexei; Mgonzo, Remi

doi:10.1002/(sici)1521-3838(199901)18:1<16::aid-qsar16>3.3.co;2-f

Cited by 2 publications

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“…If Pa > 0.7, the substance is very likely to exhibit experimental activity; if 0.5 < Pa < 0.7, the substance is likely to exhibit the activity but with less probability; If Pa < 0.5, the substance is unlikely to exhibit. However, if activity is confirmed experimentally despite low Pa value, the substance may be a 'new chemical entity' not catered for in the training of the PASS algorithm 43,44 . As can be seen from Table 3, none of the compounds is predicted to be active, or even moderately active, despite two of them being clinically proven and approved for the treatment of AD.…”

Section: Resultsmentioning

confidence: 99%

In silico and in vitro studies confirm Ondansetron as a novel acetylcholinesterase and butyrylcholinesterase inhibitor

Gholami

Minai-Tehrani

Eriksson

2023

Sci Rep

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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is growing rapidly among the elderly population around the world. Studies show that a lack of acetylcholine and butyrylcholine due to the overexpression of enzymes Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE) may lead to reduced communication between neuron cells. As a result, seeking novel inhibitors targeting these enzymes might be vital for the future treatment of AD. Ondansetron is used to prevent nausea and vomiting caused by chemotherapy or radiation treatments and is herein shown to be a potent inhibitor of cholinesterase. Comparison is made between Ondansetron and FDA-approved cholinesterase inhibitors Rivastigmine and Tacrine. Molecular docking demonstrates that interactions between the studied ligand and aromatic residues in the peripheral region of the active site are important in binding. Molecular dynamics simulations and binding pose metadynamics show that Ondansetron is highly potent against both enzymes and far better than Rivastigmine. Inhibitor activities evaluated by in vitro studies confirm that the drug inhibits AChE and BChE by non-competitive and mixed inhibition, respectively, with IC50 values 33 µM (AChE) and 2.5 µM (BChE). Based on the findings, we propose that Ondansetron may have therapeutic applications in inhibiting cholinesterase, especially for BChE.

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Section: Resultsmentioning

confidence: 99%

In silico and in vitro studies confirm Ondansetron as a novel acetylcholinesterase and butyrylcholinesterase inhibitor

Gholami

Minai-Tehrani

Eriksson

2023

Sci Rep

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“…To evaluate the applicability of the approach to the thiazole derivatives, the results of prediction are compared to experimental data for some compounds from the set, studied as 3,4,5,6,7,8,9,10,11,12,14,15,17,18,19,20,26,27,28,29 non-steroid antiinflammatory (78 compounds); local anaesthetics (6 compounds); antioxidants (5 compounds) tests. These data are given in Table II. In the experiment the compound is considered as being active if its potency is no less than the potency of the appropriate reference drug (the experimental errors are taken into account).…”

Section: Resultsmentioning

confidence: 99%

“…The structures of the synthesized compounds with numbers 1-50 is presented in our publication [20]; the structures with numbers 51 -89 are given in Table I. …”

Section: Data Setmentioning

confidence: 99%

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

Geronikaki

Lagunin

Poroikov

et al. 2002

SAR and QSAR in Environmental Research

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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.

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Computer Aided Predicting the Biological Activity Spectra and Experimental Testing of New Thiazole Derivatives

Cited by 2 publications

References 0 publications

In silico and in vitro studies confirm Ondansetron as a novel acetylcholinesterase and butyrylcholinesterase inhibitor

In silico and in vitro studies confirm Ondansetron as a novel acetylcholinesterase and butyrylcholinesterase inhibitor

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

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