A series of 9 quinolines and 18 styrylquinolines was evaluated for the drugs' in vitro antileishmanial activities and cytotoxicities. The 7-aroylstyrylquinoline scaffold appeared to be the most promising one, with the most interesting compound, no. 35, exhibiting a 50% inhibitory concentration (IC 50 ) of 1.2 M and a selectivity index value of 121.5. Compound 35 was 10-fold and 8-fold more active than miltefosine and sitamaquine, the reference compounds, with selectivity indexes 607-fold and 60-fold higher, respectively.Leishmaniasis is a family of parasitic diseases that affect about 12 million people in tropical and subtropical areas in the form of three clinical expressions: visceral leishmaniasis, which is fatal in the absence of treatment; muco-cutaneous leishmaniasis; and cutaneous leishmaniasis, which is often selfcuring. Classical drugs such as antimonials (Pentostam and Glucantime) are toxic, and drug resistance is increasing dangerously in the field (3). A liposomal amphotericin B formulation (AmBisome) less toxic than amphotericin B deoxycholate is gradually becoming the first-line therapy, especially in immunocompromised patients, but this drug must be administered by a parenteral route (11). Miltefosine (Impavido) was the first drug registered against visceral leishmaniasis in the last decade; however, its toxicity and the appearance of drug resistance justify the search for new chemical series in order to find an orally safe and active drug (8).Quinolines substituted at the 2-position have shown in vivo activities against Leishmania donovani, and many compounds have been synthesized over the last decade (14). The Drug for Neglected Diseases Initiative (DNDi) has been considering this series for evaluation in preclinical development for about a year and a half. However, although promising, the series still requires improvements, and here we report the in vitro antileishmanial evaluation of new quinoline derivatives, including 2-[2-aryl(ethenyl)]-substituted quinoline (2-styrylquinolines) bearing additional aroyl/acyl groups at the C-7 position. In addition, some compounds within this series were recently shown to display substantial antiviral activity in HIV-infected cells (13,22).The synthesis of most of the compounds has been previously reported. Briefly, Kolbe carbonation of 8-hydroxyquinaldine afforded the pivotal hydroxyacid compound 1 (9), which was further elaborated into the 5-iodoquinaldine compound 12 and amide compound 17 (13). Similarly, bromination of the C-5 position and protection of the salicylic moiety provided 5-bromoquinaldine compound 2, which was engaged in a modified Suzuki cross-coupling reaction to give 5-arylated derivatives 14 to 16 (19). Styrylquinoline compounds 19 to 27 were prepared from the corresponding quinaldine compound 3 by Perkin-type condensation in refluxing acetic anhydride, followed by hydrolysis in a pyridine-water mixture (10,16,21,22). Finally, the 7-aroyl-stryryquinoline derivatives 28 to 35 were obtained via the 7-bromostyrylquinoline compound 5 accordin...

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