Antitumor and antileishmanial activities of limonene-thiosemicarbazones bearing heterocycles nucleous

Abstract

In the present study, we provided the synthesis of a series of R-(+)- and S-(-)-limonene-based thiosemicarbazones containing different pentacyclic heterocyclic nucleus moiety focused in the search of novel antitumor and antileishmanial agents. In the antitumor assay, the derivative imidazole of S-(-)-limonene 8 was the most active compound, especially for U-251, UACC-62 and K562 human tumor cell lines with GI50 ranging from 1.0 to <0.25 µg.mL-1. On the other hand, the imidazole-thiosemicarbazone of R-(+)-limonene 4 was the most promising derivative against the promastigote form of L. amazonensis (IC50=5.9µM). Meanwhile, thiosemicarbazones without limonene moiety (9-12) showed the lowest activities in the biological assays performed. The results demonstrated the influence of the lipophilic molecular character and stereochemistry of chiral monoterpene on the evaluated activities.