Abstract
In the pursuit of novel agents for treating leishmaniasis and cancer, we have synthesized a small library of phenylcarboxamide-selenium analogs and evaluated their in vitro antileishmanial, anticancer, and carbonic anhydrase inhibitory activities. The two trifluoromethoxy-substituted aniline derivatives (3 and 6) exhibited IC(50) values in the low micromolar range in both Leishmania major and Leishmania infantum promastigotes and presented better selectivity indexes (SIs) than the reference drugs (miltefosine and paromomycin). Furthermore, all of the reported compounds displayed an outstanding antitumoral activity against a panel of 60 cancer cell lines of the National Cancer Institute's (NCI) Developmental Therapeutic Program (DTP). The cytotoxicity of compounds 1-3 in nonmalignant HaCaT cells was also evaluated. Furthermore, as several selenocompounds have previously been proven to inhibit tumor-associated human carbonic anhydrase (hCA) isoforms, all the compounds were assessed against hCA I, II, IX, and XII. Derivative 6 stood out as it inhibited tumor-associated isoform XII and the cytosolic hCA II isoform in the low micromolar range.