Synthesis of novel 5-amino-1,3,4-thiadiazole-2-sulfonamide containing acridine sulfonamide/carboxamide compounds and investigation of their inhibition effects on human carbonic anhydrase I, II, IV and VII

Burak Aday; Ramazan Ulus; Muhammet Tanç; Muharrem Kaya; Claudiu T Supuran

doi:10.1016/j.bioorg.2017.12.035

Synthesis of novel 5-amino-1,3,4-thiadiazole-2-sulfonamide containing acridine sulfonamide/carboxamide compounds and investigation of their inhibition effects on human carbonic anhydrase I, II, IV and VII

Bioorg Chem. 2018 Apr:77:101-105. doi: 10.1016/j.bioorg.2017.12.035. Epub 2018 Jan 2.

Authors

Burak Aday¹, Ramazan Ulus¹, Muhammet Tanç², Muharrem Kaya³, Claudiu T Supuran⁴

Affiliations

¹ Chemistry Department, Faculty of Arts and Science, Dumlupınar University, 43100 Kütahya, Turkey.
² Università degli Studi di Firenze, NEUROFARBA Dept., Sezione di Scienze Farmaceutiche e Nutraceutiche, 50019 Sesto Fiorentino, Florence, Italy.
³ Biochemistry Department, Faculty of Arts and Science, Dumlupınar University, 43100 Kütahya, Turkey. Electronic address: [email protected].
⁴ Università degli Studi di Firenze, NEUROFARBA Dept., Sezione di Scienze Farmaceutiche e Nutraceutiche, 50019 Sesto Fiorentino, Florence, Italy. Electronic address: [email protected].

PMID: 29353727
DOI: 10.1016/j.bioorg.2017.12.035

Abstract

Herein, we report that acridine intermediates 5 were obtained from the reduction of nitro acridine derivatives 4, which were synthesized via condensation of dimedone, p-nitrobenzaldehyde with 4-amino-N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)benzamide, respectively. Then acridine sulfonamide/carboxamide (7a-i) compounds were synthesized by reaction of amino acridine 5 with sulfonyl chlorides and carbamoyl chlorides. The new compounds were characterized by melting points, FT-IR, ¹H NMR, ¹³C NMR and HRMS analyzes. The evaluation of in vitro test of the synthesized compounds against hCA I, II, IV and VII showed that some of them are potent inhibitors. Among them, compound 7e showed the most potent activity against hCA II with a K_I of 7.9 nM.

Keywords: Acridine; Carbonic anhydrase; Carboxamide; Enzyme inhibition; Isoforms CA I, II, IV and VII; Sulfonamide.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acridines / chemistry
Acridines / pharmacology*
Carbonic Anhydrase I / antagonists & inhibitors
Carbonic Anhydrase I / metabolism
Carbonic Anhydrase II / antagonists & inhibitors
Carbonic Anhydrase II / metabolism
Carbonic Anhydrase IV / antagonists & inhibitors
Carbonic Anhydrase IV / metabolism
Carbonic Anhydrase Inhibitors / chemical synthesis
Carbonic Anhydrase Inhibitors / chemistry
Carbonic Anhydrase Inhibitors / pharmacology*
Carbonic Anhydrases / metabolism
Dose-Response Relationship, Drug
Humans
Molecular Structure
Structure-Activity Relationship
Sulfonamides / chemical synthesis
Sulfonamides / chemistry
Sulfonamides / pharmacology*
Thiadiazoles / chemical synthesis
Thiadiazoles / chemistry
Thiadiazoles / pharmacology*

Substances

Acridines
Carbonic Anhydrase Inhibitors
Sulfonamides
Thiadiazoles
5-amino-1,3,4-thiadiazole-2-sulfonamide
Carbonic Anhydrase I
Carbonic Anhydrase II
Carbonic Anhydrase IV
CA4 protein, human
Carbonic Anhydrases
carbonic anhydrase VI