Antiprotozoal Activity of Xanthone Derivatives

Abstract

A series of xanthone derivatives containing different side chains, including ω-bromo and ω-aminoalkoxylxanthones (with linear alkoxy chains of 3, 4 and 5 carbon atoms and methyl, propyl, tert-butylamino and piperidinyl moieties), synthesized from the natural xanthone lichexanthone were tested for their antiprotozoal activities against Leishamania braziliensis, L. major and Trypanosoma cruzi (extra and intracellular forms). The ω-aminoalkoxylxanthones showed good antileishmanial activity, with IC₅₀ ranging from 62.8 to 0.1 µM for promastigotes and 119.3 to 2.4 µM for amastigotes. In general, compounds with longer alkyl chains and tert-butylamino moiety showed better activity. The cytotoxicity on VERO cells was also described for some derivatives. Compound 15 (tert-butylaminobutyloxy side chain) was the most active on promastigote forms (IC₅₀ 0.1 µM), compound 16 (tert-butylaminopentyloxy side chain) sowed the best activity for amastigotes (IC₅₀ 2.4 µM) and derivative 13 (dipropylaminopentyloxy side chain) was the most selective (selectivity index of 9.4). Regarding trypanocidal activity, 16 and other groups of derivatives, (ω-bromoalkoxylxanthones, prenyl and epoxyl side chains) had moderate to good activity on T. cruzi trypomastigotes, with IC₅₀ ranging from 30.6 to 4.1 µM, while only two ω-aminoalkoxylxanthones (10 and 11) were weakly active against T. cruzi amastigotes.

DOI: http://dx.doi.org/10.17807/orbital.v12i3.1460