New Se-Compounds With Antileishmanial, Antitumor, and Carbonic Anhydrase Inhibitory Properties

Area of Science:

• Medicinal Chemistry
• Parasitology
• Oncology
• Biochemistry

Background:

• Leishmaniasis and cancer are significant global health challenges requiring novel therapeutic agents.
• Phenylcarboxamide-selenium analogs are explored for their potential biological activities.
• Human carbonic anhydrases (hCAs) are implicated in cancer progression and are potential therapeutic targets.

Purpose of the Study:

• To synthesize and evaluate phenylcarboxamide-selenium analogs for antileishmanial and anticancer activities.
• To assess the inhibitory effects of these compounds on human carbonic anhydrase (hCA) isoforms.
• To determine the selectivity of active compounds against cancer cells versus normal cells.

Main Methods:

• Synthesis of a small library of phenylcarboxamide-selenium analogs.
• In vitro evaluation of antileishmanial activity against Leishmania major and Leishmania infantum.
• In vitro anticancer screening against a panel of 60 cancer cell lines (National Cancer Institute's DTP).
• Cytotoxicity assessment in nonmalignant HaCaT cells.
• Inhibition assays against human carbonic anhydrase isoforms (hCA I, II, IX, and XII).

Main Results:

• Two trifluoromethoxy-substituted aniline derivatives (compounds 3 and 6) showed low micromolar IC50 values against Leishmania promastigotes, with better selectivity indexes than reference drugs.
• All synthesized compounds exhibited significant antitumoral activity across a broad spectrum of cancer cell lines.
• Compound 6 demonstrated potent inhibition of tumor-associated hCA XII and cytosolic hCA II isoforms in the low micromolar range.

Conclusions:

• Phenylcarboxamide-selenium analogs represent a promising class of compounds for developing new treatments for leishmaniasis and cancer.
• Compound 6 is a particularly promising candidate due to its dual activity against parasites, cancer cells, and specific hCA isoforms.
• The inhibition of hCA isoforms by these selenium compounds warrants further investigation for therapeutic applications.