Thiosemicarbazone-benzenesulfonamide Derivatives as Human Carbonic Anhydrases Inhibitors

What is it about?

Carbonic anhydrases (CAs) are enzymes that are found throughout the body and are involved in converting carbon dioxide (CO2) to bicarbonate (HCO3-). Inhibiting these enzymes selectively has shown promise in developing new drugs for various diseases. We created a series of new compounds containing thiosemicarbazones and tested their ability to inhibit specific human carbonic anhydrase enzymes (hCA I, II, IX, and XII) using a single tail approach. The compounds generally showed strong inhibition of the enzymes, with compound 6b being particularly effective against hCA I, II, IX, and XII. Compound 6e also showed significant inhibition against these enzymes. We conducted molecular docking studies to better understand how the compounds interact with the enzymes and found insights into their binding mechanisms and selectivity.

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Photo by Giovanni Crisalfi on Unsplash

Photo by Giovanni Crisalfi on Unsplash

Why is it important?

We conducted structural modification of SLC-011, the only CA inhibitor in clinical phase II trial, using bioisosterism and elongation of tail-approach to improve the activity against CA isoenzymes. The result showed that our modification led to low nanomolar inhibition of the enzymes, especially hCA II.

Perspectives