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Substituted thiadiazines as potential anti‐stress agents. Results of (Q)SAR prediction and experiments in vivo
Author(s) -
Sarapultsev Alexey P,
Sarapultsev Petr A,
Sidorova Larisa P,
Poroikov Vladimir V,
Chupakhin Oleg N
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.938.5
Subject(s) - in vivo , pharmacology , chemistry , drug , anxiolytic , medicine , biochemistry , biology , receptor , microbiology and biotechnology
The goal of the study was the prediction and experimental confirmation of anti‐stress action of the compounds from the group of substituted thiadiazines. Virtual screening of biological effects and potential targets of action of the compounds was performed using computer program PASS ( www.way2drug.com ). PASS is the program for prediction of biological activity for drug‐like substances on the basis of structural formulas – (Q)SAR. Pharmacological evaluation was conducted in according to E.F. Lavretskaya (1985) and R.U. Ostrovskaya (2012) guidelines. According to the previous results, the L17 compound (6H‐1,3,4‐Thiadiazine, 5‐(3‐bromophenyl)‐2‐(4‐morpholinyl)) inhibited apoptosis, supported and strengthened lymphopoiesis in the thymus caused by immobilization stress, lowered glucose levels and ACT. Those studies enabled us to suggest that L17 compound lowered the reaction to stress. PASS prediction of biological effects showed that the test compounds had a similar structure with four groups of drugs: anxiolytic agents (tranquilizers), general anesthetics, anti‐inflammatory agents and antineurotic drugs. According to the results of pharmacological evaluation in vivo , substituted thiadiazine‐amines possessed a combination of properties of choline‐, adrenergic‐ and serotonin blockers which was also confirmed by the results of computer evaluation. Thus, the results of the study described substituted thiadiazines as potential anti‐stress agents. Support or Funding Information The work was done in the framework of the Russian State Academies of Sciences, Fundamental Research Program for 2013–2020 and was supported by a Special Research Grant of Ural Branch of RAS, Ekaterinburg, Russia (15‐3‐4‐27).The leading compound L17 (6H‐1,3,4‐Thiadiazine,5‐(3‐bromophenyl)‐2‐(4‐morpholinyl).