A perspective on quantitative structure-activity relationships and carbonic anhydrase inhibitors

Area of Science:

• Biochemistry and Medicinal Chemistry
• Enzymology
• Pharmacology

Background:

• Carbonic anhydrases (CAs) are a family of enzymes with diverse physiological and pathophysiological roles.
• CA inhibitors, particularly sulfonamides, are clinically used for glaucoma and neuromuscular disorders.
• Emerging research highlights the involvement of CAs and their inhibitors in cancer therapy.

Purpose of the Study:

• To review quantitative structure-activity relationship (QSAR) studies of carbonic anhydrase inhibitors.
• To focus on the application of physical and quantum theoretical descriptors in QSAR for CA inhibitors.
• To explore the potential of CA inhibitors as anticancer agents.

Main Methods:

• Review of literature on carbonic anhydrase inhibitors and QSAR studies.
• Analysis of physical descriptors (e.g., partition coefficients, Hammett constants).
• Analysis of quantum theoretical descriptors (e.g., orbital energies, atomic charges, polarizabilities).

Main Results:

• Detailed understanding of CA catalytic and inhibition mechanisms aids inhibitor design.
• Sulfonamide-based CA inhibitors show promise as novel anticancer therapies.
• QSAR studies utilize various descriptors to correlate chemical structure with biological activity.

Conclusions:

• Carbonic anhydrase inhibitors represent a promising avenue for cancer treatment.
• Physical and quantum descriptors are valuable tools in developing potent and selective CA inhibitors.
• Further QSAR investigations can accelerate the discovery of new therapeutic agents targeting CAs.