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

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


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.


Funder: King Saud University, Riyadh, Saudi Arabia


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

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J Enzyme Inhib Med Chem

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