Synthesis and biological evaluation of novel 3-(quinolin-4-ylamino)benzenesulfonamides as carbonic anhydrase isoforms I and II inhibitors

Mohammad M Al-Sanea,Ahmed Elkamhawy,Sora Paik,Silvia Bua,So Ha Lee,Mohamed A Abdelgawad,Eun Joo Roh,Wagdy M Eldehna,Claudiu T Supuran

doi:10.1080/14756366.2019.1652282

Abstract

Carbonic anhydrases (CAs, EC 4.2.1.1) are crucial metalloenzymes that are involved in diverse bioprocesses. We report the synthesis and biological evaluation of novel series of benzenesulfonamides incorporating un/substituted ethyl quinoline-3-carboxylate moieties. The newly synthesised compounds were in vitro evaluated as inhibitors of the cytosolic human (h) isoforms hCA I and II. Both isoforms hCA I and II were inhibited by the quinolines reported here in variable degrees: hCA I was inhibited with KIs in the range of 0.966–9.091 μM, whereas hCA II in the range of 0.083–3.594 μM. The primary 7-chloro-6-flouro substituted sulphfonamide derivative 6e (KI = 0.083 μM) proved to be the most active quinoline in inhibiting hCA II, whereas, its secondary sulfonamide analog failed to inhibit the hCA II up to 10 μM, confirming the crucial role of the primary sulphfonamide group, as a zinc-binding group for CA inhibitory activity.

Highlights

Carbonic anhydrases (CA) (CAs, EC 4.2.1.1) are zinc-containing metalloenzymes that are present in most organisms all over the tree of life[1,2]
We report a new series of primary benzenesulfonamides incorporating un/substituted ethyl quinoline-3carboxylate (6a–6f, Figure 1) as well as the secondary benzenesulfonamide analogue (11, Figure 1), with the prime goal of CONTACT Mohammad M
The NMR spectra were obtained on Bruker Avance 400 (400 MHz 1H and 101 MHz 13 C NMR). 1H NMR spectra were referenced to tetramethylsilane (d 1⁄4 0.00 ppm) as an internal standard and were reported as follows: chemical shift, multiplicity (b 1⁄4 broad, s 1⁄4 singlet, d 1⁄4 doublet, t 1⁄4 triplet, dd 1⁄4 doublet of doublet, m 1⁄4 multiplet)

Summary

Introduction

Carbonic anhydrases (CA) (CAs, EC 4.2.1.1) are zinc-containing metalloenzymes that are present in most organisms all over the tree of life[1,2]. We report a new series of primary benzenesulfonamides incorporating un/substituted ethyl quinoline-3carboxylate (6a–6f, Figure 1) as well as the secondary benzenesulfonamide analogue (11, Figure 1), with the prime goal of CONTACT Mohammad M.

Results

Conclusion