Synthesis, Characterization and In-vitro Antifungal Evaluation of Some Dithiocarbamic Acid Derivatives

Some new N, N‐disubstituted dithiocarbamates derived from α‐acetonaphthone and their precursors, potassium salts of dithiocarbamic acid, were prepared and evaluated for antifungal activity. Synthesis involved the reaction of α‐chloro‐2‐acetonaphthone or α‐chloro‐4‐methoxy‐1‐acetonaphthone with the potassium salts of N, N‐disubstituted dithiocarbamic acid (5a‐g). Compounds 5a‐g were readily produced by reaction of equivalent amounts of the appropriate secondary amine, potassium hydroxide and carbon disulphide. The purity of the final derivatives, N, N‐disubstituted dithiocarbamates 6a‐g and 7a‐g, was determined by elemental analyses and TLC, and assignment of structures was confirmed by IR, 1H NMR,13C NMR and MS. Preliminary evaluation of the antifungal activity of derivatives 5a‐g, 6a‐g and 7a‐g was determined in‐vitro at a 2.5 or 5.0% concentration against different fungal species using tolnaftate as a reference drug. The potassium salts 5a‐g were the most potent derivatives of the tested series. Compounds 5a‐e showed significant broad spectrum antifungal activity. Combination of the dithiocarbamate with acetonaphthonyl moiety, represented by the 6a‐g and 7a‐g series, resulted in a decrease in or complete loss of antifungal activity in certain derivatives. Compounds derived from 4‐methoxy‐1‐aceto‐naphthone (7a‐g) were generally superior to their 4‐nonsubstituted congeners (6a‐g). The morpholino dithiocarbamate derivative 7e was equipotent or superior to the reference drug against the tested dermatophytes species and Rhodotorula rubra at a 5% concentration. In addition, 7e exhibited inhibitory activity against Chrysosporium tropicum, Emericella nidulans, Penicillium aurantiogriseum and Aspergillus sydowii. Some derivatives of both series showed selective activity against certain fungi, (e.g. 6f against Phoma glomerata and Scopulariopsis acremonium; 6g against Emericella nidulans and Phoma glomerata; 7c against Geotrichum candidum and Mucor circinelloides; 7d against Geotrichum candidum, Penicillium aurantiogriseum and Rodotorula rubra and 7f against Mucor circinelloides).