On the Effect of the Nature of Substituents on the Antimicrobial Activity of Water-Soluble Acylhydrazones on the Isatin
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On the Effect of the Nature of Substituents on the Antimicrobial Activity of Water-Soluble Acylhydrazones on the Isatin Scaffold A. V. Bogdanova,*, A. D. Voloshinaa, A. R. Khamatgalimova, N. V. Terekhovaa, and Corresponding Member of the RAS V. F. Mironova Received June 23, 2020; revised July 6, 2020; accepted September 2, 2020
Abstract—The dependence of the level of antimicrobial activity of some ammonium isatin-3-acylhydrazones on the sterical hindrance and electronic nature of substituents in the benzyl moiety was elucidated using simple molecular descriptors and quantum chemical calculations. The structure and electronic nature of substituents in position 1 and the lipophilicity of compounds of this series were shown to be the key factors determining the activity. Keywords: antimicrobial activity, hydrazones, heterocycles, structure–activity, isatin DOI: 10.1134/S0012500820090013
The oxindole heterocyclic scaffold is encountered in many biologically active compounds and refers to the class of “privileged structures” [1]. Among a large variety of compounds containing this structural moiety, isatin (indoline-2,3-dione) is being studied most intensively. Easy modification of the carbonyl group, the aromatic moiety, and the nitrogen atom provides broad opportunities and prospects for applications in medicine, organic synthesis, and the chemistry of functional materials [2–6], including the possibility to control the properties of its derivatives by modification of a particular reaction center. Numerous isatin derivatives are known to exhibit various types of biological activity such as anticancer [7], antituberculosis [8], antimicrobial [9], and fungicidal activities [10]. Isatin5-sulfonamides, which are able to inhibit caspases, key apoptotic enzymes, are highly popular derivatives of this type. Functionalization of the oxindole ring with a hydrazone moiety often gives rise to new kinds of activity (Scheme 1). It is noteworthy that the structure of substituents at the periphery of the heterocyclic scaffold has a considerable influence on the level and type of the physiological action. In this context, a major problem preventing conduction of a larger range of biological assays is poor solubility of the target compounds in biocompatible solvents, first of all, in water. A possible solution is to introduce a salt group into the molecule of an isatin a Arbuzov
Institute of Organic and Physical Chemistry, Federal Research Center “Kazan Scientific Center of Russian Academy of Sciences,” Kazan, 420088 Russia *e-mail: [email protected]
derivative. Possible sources of such groups are Girard reagents, that is, hydrazides containing a positively charged nitrogen atom. Owing to the high reactivity of the carbonyl group in the 3-position of isatin, it is possible to develop an approach to the synthesis of water-soluble ammonium isatin-3-acylhydrazones [11–14]. Antimicrobial activity studies attest to a high potential of several series of these compounds in the design and search of efficient and non-toxic antimicrobi
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