Biological Activity Evaluation of Phenolic Isatin-3-Hydrazones Containing a Quaternary Ammonium Center of Various Structures

Abstract

A series of new isatin-3-hydrazones bearing different ammonium fragments was synthesized by a simple and easy work-up reaction of Girard's reagents analogs with 1-(3,5-di-tert-butyl-4-hydroxybenzyl)isatin. All derivatives have been shown to have antioxidant properties. In terms of bactericidal activity against gram-positive bacteria, including methicillin-resistant strains of Staphylococcus aureus, the best compounds are 3a, 3e, and 3m, bearing octyl, acetal, and brucine ammonium centers, respectively. In addition, brucine and quinine derivatives 3l, and 3j exhibit platelet antiaggregation activity at the level of acetylsalicylic acid, and this series of isatin derivatives does not adversely affect the hemostasis system as a whole. Thus, all the obtained results can lay the groundwork for future pharmaceutical developments for the creation of effective antibacterial drugs with reduced systemic toxicity due to the presence of antioxidant properties.

Keywords: antioxidants; cytotoxicity; hemostasis; hydrazones; isatin; quaternary ammonium compounds.

Figure 1

Representatives of isatin acylhydrazones with different bioactivities.

Figure 2

Previously published phenolic isatin hydrazones with antimicrobial activity [25,26,27].

Scheme 1

Two-step synthesis of ammonium acetohydrazides.

Scheme 2

Synthesis of isatin hydrazones containing an ammonium center of various structures.

Scheme 3

New isatin-3-acylhydrazones based on brucine alkaloid.

Figure 3

Hemotoxic and cytotoxic activity of 3a–3n, expressed in terms of HC₅₀ и IC₅₀; * Values indicate p < 0.01.

Figure 4

Summary of biological activity data of phenolic isatin-3-hydrazones.