New Ketene Dithioacetals Generated from 2-Nitroperchlorobutadiene and Investigation of Their Antibacterial, Antifungal, Anticonvulsant and Antidepressant Activities

Abstract

The ketene dithioacetal 3 generated from 2-nitroperchlorobutadiene 1 reacted with various heterocyclic amines and aliphatic, aromatic and heterocyclic thiols to produce functionalized new ketene-N,S,S-acetals and S,S,S-acetals 4a-f, 5a-h as heterocyclic dithiolanes. They were separated/purified by chromatographic methods and their exact structure characterization were made clear by spectroscopic methods. These compounds synthesized could act as effective drugs for versatile activity. Evaluation of the antimicrobial effect of the obtained substances determined derivatives 4e and 5h, which have MIC=15.6 mu g/mL for the test culture of Mycobacterium luteum bacteria closing to the control drug Vancomycin. The obtained compounds can be proposed as a promising synthetic objects for future molecular design to enhance the antimicrobial action. Ketene dithioacetals 3, 4a, 4b, 4e, 5g (50 mg/kg) exhibited antiseizure effect comparable with reference drug (valproic acid) on the model of pentylenetetrazole-induced convulsions after single oral administration both at 3 h and 24 h. Furthermore, tested dithioacetals possessed prolonged antidepressant activity in forced swim test (FST) considerable decreasing the duration of immobility time compared to reference drug amitriptyline. This is the first study of the investigation of anticonvulsant and antidepressant activities of ketene dithioacetals.