Ketoconazole-carbonic anhydrase inhibitors as potential anticancer agents

Area of Science:

• Oncology
• Biochemistry
• Pharmacology

Background:

• Cancer's biochemical complexity allows repurposing drugs for new therapies.
• Ketoconazole (KTZ) shows potential in oncology by suppressing steroidogenesis and disrupting extracellular vesicle (EV) biogenesis.

Purpose of the Study:

• To investigate the anticancer effects of compounds integrating a Carbonic Anhydrase (CA) IX/XII inhibiting warhead with Ketoconazole (KTZ).
• To explore the dual-mechanism therapeutic potential of these novel compounds.

Main Methods:

• Synthesized and tested compounds with CA IX/XII inhibiting warheads and KTZ.
• Evaluated in vitro antiproliferative effects on various tumoral cell lines.
• Assessed the impact on EV pathways.

Main Results:

• Compounds demonstrated in vitro antiproliferative effects on tumoral cell lines.
• The observed effects are attributed to the combined action of anti-CA IX/XII activity and EV pathway disruption.
• This represents the first evidence of such a dual-mechanism approach.

Conclusions:

• The novel compounds exhibit promising dual-mechanism anticancer activity.
• Integration of anti-CA IX/XII effects with EV pathway disruption offers a novel therapeutic strategy.
• These findings suggest a potential new avenue for cancer treatment.