Síntese de derivados benzoxazólicos, potenciais agentes anti-Leishmania e inibidores de proteases

Abstract

Leishmaniasis is a disease found in various regions in the world, and thousands of cases are recorded each year in Brazil. Caused by protozoa of the genus Leishmania and transmitted by the infected sandfly, it can cause visceral or cutaneous infections to develop depending on the species. Intense investigations in host-parasite interaction enabled the discovery of new targets of action, such as proteases that have high profile, since they are essential for survival and proliferation of the parasites. There are reports of natural and synthetic benzophenones as well as derivatives containing acetophenone core, and other ketone derivatives containing heterocycles in their structures, which have protease inhibitory and anti-leishmanial activity. Thus, benzophenone and acetophenone-based benzoxazoles were obtained and characterized, and evaluated for their anti-leishmanial and protease inhibitory activities. Ten final benzoxazoles derivatives were obtained, and all were characterized by infrared and ¹H and ¹³C nuclear magnetic resonance spectroscopies. All compounds were submitted to in vitro testing to evaluate their activity against the promastigote form of Leishmania amazonensis. The derivatives 22e and 24b showed good activity with IC50 values of 90.3 and 130.9 μM, respectively; and the starting benzophenone (23a) and its nitro derivative 24a, had IC50 values of 190.9 and 158.4 μM, respectively. In addition, compounds 22e, 24 and 23a were evaluated for their inhibitory activities of papain and trypsin as model proteases, and were found to be more active against papain, with IC50 values more satisfactory than the standard inhibitor used.