Synthesis and Evaluation of Thiazolidinone-Isatin Hybrids for Selective Inhibition of Cancer-Related Carbonic...

Area of Science:

• Medicinal Chemistry
• Biochemistry
• Oncology

Background:

• Human carbonic anhydrase (hCA) isoforms IX and XII are overexpressed in cancer cells.
• These hCA isoforms play critical roles in tumor metastasis and cancer therapeutic response.
• Targeting hCA IX and XII offers a promising strategy for cancer treatment.

Purpose of the Study:

• To design, synthesize, and evaluate novel thiazolidinone-based sulfonamide derivatives.
• To identify potent and selective inhibitors of hCA IX and hCA XII.
• To explore the potential of molecular hybridization for developing anticancer agents.

Main Methods:

• Molecular hybridization approach combining antitumor moieties.
• Synthesis of a library of thiazolidinone-sulfonamide derivatives.
• In vitro biological evaluation of inhibitory activity against hCA I, II, IX, and XII isoforms.

Main Results:

• Several synthesized compounds exhibited promising inhibitory activities against hCA isoforms.
• Compounds showed selectivity, effectively inhibiting hCA IX and XII while sparing hCA I and II.
• Compound 3h demonstrated high selectivity and potent inhibition with K_i values of 57.8 nM (hCA IX) and 44.3 nM (hCA XII).

Conclusions:

• Thiazolidinone-based sulfonamides are effective inhibitors of cancer-relevant hCA isoforms.
• Compound 3h represents a highly selective and potent lead compound for further anticancer drug development.
• The molecular hybridization strategy proved successful in optimizing inhibitor profiles.