Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Investigation of Novel Thiazole Derivatives Bearing the Benzenesulfonamide Moiety as MAO Inhibitors with a Promising Activity Profiles

Anton A. Shetnev
* ORCID logo ,
Julia A. Efimova
,
Gasilina A Olga
,
Shabalina J. Eugenia
,
Lifanov A Dmitry
,
Petersen V Elena
,
Mikhail K. Korsakov
,
Anél Petzer
,
Jacobus P. Petzer
Version 1 : Received: 19 November 2023 / Approved: 21 November 2023 / Online: 21 November 2023 (10:47:16 CET)

How to cite: Shetnev, A.A.; Efimova, J.A.; Olga, G.A.; Eugenia, S.J.; Dmitry, L.A.; Elena, P.V.; Korsakov, M.K.; Petzer, A.; Petzer, J.P. Investigation of Novel Thiazole Derivatives Bearing the Benzenesulfonamide Moiety as MAO Inhibitors with a Promising Activity Profiles. Preprints 2023, 2023111294. https://doi.org/10.20944/preprints202311.1294.v1 Shetnev, A.A.; Efimova, J.A.; Olga, G.A.; Eugenia, S.J.; Dmitry, L.A.; Elena, P.V.; Korsakov, M.K.; Petzer, A.; Petzer, J.P. Investigation of Novel Thiazole Derivatives Bearing the Benzenesulfonamide Moiety as MAO Inhibitors with a Promising Activity Profiles. Preprints 2023, 2023111294. https://doi.org/10.20944/preprints202311.1294.v1

Abstract

We have recently reported that a series of 1,3,4-oxadiazol-2-ylbenzenesulfonamides acts as potent and specific monoamine oxidase B (MAO-B) inhibitors with some compounds possessing potencies in the nanomolar range. While sulfonamide compounds (e.g., zonisamide) have been reported to inhibit the MAO enzymes, nanomolar MAO inhibition potencies for this class are not frequently observed. The present study expanded on these findings by replacing the 1,3,4-oxazole moiety with a 1,3-thiazole heterocycle. A series of 23 primary sulfonamides were synthesized by reaction of an α-haloketone with a substituted carbothioamide. The results of the MAO inhibition studies showed that the 1,3-thiazolylbenzenesulfonamides were specific inhibitors of human MAO-B. The most potent MAO-B inhibitor exhibited an in vitro IC50 value of 0.103 µM (3j). The derivatives were, however, weaker inhibitors of human MAO-A with the most potent compound exhibiting an IC50 value of 11.9 µM (3a). Examination of the structure-activity relationships (SARs) showed that the most potent MAO-B inhibition was obtained with substitution of the sulfonamide on the meta position of the phenyl rather than the para position. This study concludes that 1,3-thiazolylbenzenesulfonamides represent a class of potent and specific MAO-B inhibitors, which may serve as leads for the development of new treatments for disease states such as Parkinson’s disease.

Keywords

inhibition; monoamine oxidase; MAO; thiazole; sulfonamide; SAR; synthesis

Subject

Chemistry and Materials Science, Medicinal Chemistry

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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