Disubstituted thiourea derivatives and their activity on CNS: Synthesis and biological evaluation

A series of new thiourea derivatives of 1,2,4-triazole have been synthesized. The difference in structures of obtained compounds are directly connected with the kind of isothiocyanate (aryl/alkyl). The 1H NMR, 13C NMR, MS methods were used to confirm structures of obtained thiourea derivatives. The molecular structure of (1, 17) was determined by an X-ray analysis. Two of the new compounds (8 and 14) were tested for their pharmacological activity on animal central nervous system (CNS) in behavioural animal tests. The results presented in this work indicate the possible involvement of the serotonergic system in the activity of 8 and 14. In the case of 14 is also a possible link between its activity and the endogenous opioid system. All obtained compounds were tested for antibacterial activity against Gram-positive cocci, Gram-negative rods and antifungal activity. Compounds (1, 2, 5, 7, 9) showed significant inhibition against Gram-positive cocci. Microbiological evaluation was carried out over 20 standard strains and 30 hospital strains. Selected compounds (1–13) were examined for cytotoxicity, antitumor, and anti-HIV activity.

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► New thiourea derivatives of 4H-1,2,4-triazol-3-amine were synthesized.
► Pharmacological activity on CNS in behavioural animal tests was evaluated.
► The results indicate the possible involvement of the serotonergic system in the activity.
► Antimicrobial, cytotoxicity, antitumor, and anti-HIV activity was tested.
► For five compounds significant inhibition against Gram-positive cocci was found.