New 4-iminohydantoin sulfamide derivatives with antiviral and anticancer activity

Yurii Kornii,Oleh Shablykin,Olga Shablykina,Volodymyr Brovarets

doi:10.15407/bioorganica2021.01.010

Abstract

A number of sulfamides were obtained by reaction of (5-(dichloromethylene)-2-oxoimidazolidin-4-ylidene)sulfamoyl chloride with anilines, benzylamines, Boc-protected piperazine, methylalylamine, and amino acids methyl esters with primary and secondary amino group. The antiviral and anticancer activity of new derivatives was evaluated. The most effective compounds against Human cytomegalovirus were sulfamides based on anisidine (1b), N-Boc-piperazine (1h), and the derivatives 1n,o with fragments of nipecotic and azetidine-3-carboxylic acids, respectively. Anticancer activity was most significant for sulfamides based on p-methoxybenzylamine (compound 1d), benzylmethylamine (compound 1f), and allylmethylamine (compound 1g).

Highlights

The hydantoin motif often appears in bioactive molecules of both natural and synthetic origin (Figure 1) [1,2]
We have significantly expanded the list of amines that were involved in the interaction with sulfamoyl chloride 2 to obtain the target
The focus on a series of amino acid derivatives obtaining was due to previous results: a sulfamide of similar structure with a residue of ester nipecotic acid showed strong anticancer activity [10], and the corresponding acid exhibited antiviral action [11]

Summary

Introduction

The hydantoin motif often appears in bioactive molecules of both natural and synthetic origin (Figure 1) [1,2] This heterocyclic system, due to its low aromaticity, can be consider as a cyclic combination of an α-amino acid and urea with all the resultant consequences, such as the possibility of assembly with a variation of substituents [3], the relative ease of combinatorial libraries creation [4], the possibility of further modification, as well as bioavailability and environmental friendliness [5]. The creation of new substances with a hydantoin fragment and Received: Revised: Accepted: Published online:

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Conclusion