ASSESSMENT OF ANTIFUNGAL ACTIVITY OF SOME PYRROLIDINONES AND CONDENSED AZEPINONES
DOI:
https://doi.org/10.32782/pcsd-2022-3-5Keywords:
pyrrolidinones, azepinones, antifungal activity, bioscreening, cyclization, amides of styrylacetic acids, polyphosphoric acid, arylsulfenyl chloridesAbstract
The work is devoted to the study of the antifungal activity of some derivatives of pyrrolidinones and condensed azepinones obtained as a result of electrophilic intramolecular cyclization of N-unsubstituted, N-alkyl-, N-aryl- and N-heterylamides of styrylacetic acids with different substituents in the styrene part of the molecule under the action of polyphosphoric acid and arylsulfenyl chlorides, as effective electrophilic reagents for the mentioned substrates. The introductory part of the article reveals the importance of amides of unsaturated carboxylic acids for the construction of biologically active heterocyclic substrates, which are promising for the search for bioregulators of a wide spectrum of action. The general scheme for obtaining 1-unsubstituted and 1-substituted 5-aryl(heteryl)pyrrolidin-2-ones, 2H-benzazepin- 2-ones, 2H-naphtho[1,2-b]-, 2H-naphtho[2,1 -b]- and 2H-naphtho[2,3-b]azepin-2-ones and 5H-thieno[3,2-b]azepin-5- ones and their sulfonyl derivatives. Antifungal activity was evaluated by the value of the minimum fungistatic concentration (MfsK) in relation to a number of yeast-like fungi (Asp. fumigatus K 11, Asp. niger K 9, Asp. amstelodami K12, Tr. mentagrophytes var. interdigitale and Tr. interdigitale ATCC 9533). The obtained results show that the minimum fungistatic concentration for the studied compounds varies widely (MfsK = 3.90-125 μg / ml). Among the spectrum of used strains of microorganisms, the latter were more selective for the fungus Asp. fumigatus K 11, in particular for compounds 1d,e and 2d, the minimum fungistatic concentration is 3.90 μg/ml, which is at the level of the antifungal drug "Mycospor", which was used as a control. The obtained results prove the perspective and feasibility of using electrophilic intramolecular cyclization of amides of styroacetic acids to obtain new effective antifungal drugs.
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