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Enaminone-based carboxylic acids as novel non-classical carbonic anhydrases inhibitors: design, synthesis and in vitro biological assessment.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Abo-Ashour, Mahmoud F 
Almahli, Hadia 
Bonardia, Alessandro 
Khalil, Amira 
Al-Warhi, Tarfah 

Abstract

In searching for new molecular drug targets, Carbonic Anhydrases (CAs) have emerged as valuable targets in diverse diseases. CAs play critical functions in maintaining pH and CO2 homeostasis, metabolic pathways, and much more. So, it is becoming attractive for medicinal chemists to design novel inhibitors for this class of enzymes with improved potency and selectivity towards the different isoforms. In the present study, three sets of carboxylic acid derivatives 5a-q, 7a-b and 12a-c were designed, developed and evaluated for the hCA inhibitory effects against hCA I, II, IX and XII. Compounds 5l, 5m, and 5q elicited the highest inhibitory activities against hCA II, IX and XII. In summary, structural rigidification, regioisomerism and structural extension, all played obvious roles in the degree of hCA inhibition. This present work could be a good starting point for the design of more non-classical selective hCA inhibitors as potential targets for several diseases.

Description

Funder: King Saud University, Riyadh, Saudi Arabia

Keywords

Carbonic anhydrase, H-NMR, enaminone, stopped-flow assay, Antigens, Neoplasm, Carbonic Anhydrase IX, Carbonic Anhydrase Inhibitors, Carbonic Anhydrases, Carboxylic Acids, Molecular Structure, Structure-Activity Relationship

Journal Title

J Enzyme Inhib Med Chem

Conference Name

Journal ISSN

1475-6366
1475-6374

Volume Title

37

Publisher

Informa UK Limited
Sponsorship
Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia (RSP-2021/103)
Princess Nourah bint Abdulrahman University Researchers Supporting Project (PNURSP2022R25)