Isatin: a privileged scaffold for the design of carbonic anhydrase inhibitors

Claudia Melis,Rita Meleddu,Andrea Angeli,Simona Distinto,Giulia Bianco,Clemente Capasso,Filippo Cottiglia,Rossella Angius,Claudiu T Supuran,Elias Maccioni

doi:10.1080/14756366.2016.1235042

Abstract

The isatin scaffold is the constitutive fragment of several natural and synthetic bioactive molecules. Albeit several benzene sulphonamide-based carbonic anhydrase inhibitors (CAIs) have been reported, only recently isatin benzene sulphonamides have been studied and proposed as CAIs. In this study we have designed, synthesised, and evaluated the biological activity of a series of differently substituted isatin-based benzene sulphonamides which have been designed for the inhibition of carbonic anhydrase isoforms. The activity of all the synthesised compounds was evaluated towards human carbonic anhydrase I, II, IX, and XII isozymes. Our results indicate that the nature and position of substituents on the isatin ring can modulate both activity and isozyme selectivity.

Highlights

The isatin nucleus could be considered as a privileged scaffold for the design of biologically active agents
The first step is the synthesis of the 4-sulphamoylphenyl-thiourea derivative (1 of Figure 2) by simple reaction of the 4-aminobenzensulphonamide with methylisothiocyanate
Desired compounds were obtained by reacting compound 2 with the appropriate isatin

Summary

Introduction

The isatin nucleus could be considered as a privileged scaffold for the design of biologically active agents. The design of isatin-based carbonic anhydrase inhibitors (CAIs) has been reported[10,11,18,19,20]. On the basis of the above and with the aim to achieve structure-activity relationships on isatin derived CAIs, we have designed and synthesised a series of new 4-{[5–(2-oxo-2,3-dihydro-1H-indol3-ylidene)-3-methyl-4-oxo-1,3-thiazolidin-2-ylidene]amino}benzene-1sulphonamides as potential inhibitors of the tumour associated CA isoforms IX and XII.

Results

Conclusion