Antichagasic and trichomonacidal activity of 1-substituted 2-benzyl-5-nitroindazolin-3-ones and 3-alkoxy-2-benzyl-5-nitro-2H-indazoles

Antichagasic, Leishmanicidal, and Trichomonacidal Activity of 2‐Benzyl‐5‐nitroindazole‐Derived Amines

“…Within the area of new potential antichagasic drugs, we recently described the synthesis and activity of many 5‐nitroindazole derivatives. In direct relationship to the current work, we highlighted interesting results found for several 1,2‐disubstituted indazolin‐3‐ones . The trypanocidal properties of some 3‐alkoxy‐1‐alkylindazoles were also reported …”

“…With regard to the potent antichagasic activity of 1,2‐disubstituted 5‐nitroindazolin‐3‐ones (Figure , series A ), we initially found that a 2‐benzyl group was the most convenient substituent for optimized activity within these compounds and, in further investigations, that alkenyl and many ω‐substituted alkyl groups were accepted at position 1 without affecting antitrypanosomal properties. The most active compounds against T. cruzi amastigotes from our previous studies ( 1 – 5 ; IC 50 =0.22–0.54 μ m ) are shown in Figure …”

“…Regarding trichomonacidal activity, we previously found that some 3‐alkoxy‐2‐benzyl‐2 H ‐indazoles (series B ) displayed activity against T. vaginalis trophozoites. Representative examples of the most efficient compounds are also included in Figure ( 6 and 7 ; IC 50 =9.82 and 7.25 μ m , respectively).…”

Activity of 2-benzyl-1-(2-hydroxyethyl)-5-nitroindazolin-3-one on Trypanosoma cruzi Bloodstream Trypomastigotes (Y strain): In Vitro and In Vivo Studies

“…In this context, our group has proposed 5-nitroindazole derivatives as antichagasic prototypes, according to their activity in vitro and in vivo [1][2][3][4][5]. The lack of cytotoxicity and outstanding activity on the replicative forms of Trypanosoma cruzi (i.e., epimastigotes and intracellular amastigotes) previously shown by 2-benzyl-1-(2-hydroxyethyl)-5-nitroindazolin-3-one [5], encouraged assaying this compound in vitro on bloodstream trypomastigotes of Y strain (DTU TcII) and then, moved it to murine models of toxicity and infection. After confirming NOAEL >25 mg/kg and no signs of acute toxicity (i.e., normal weight, organs appearance, hemogram and biochemistry), infected mice were treated on the 5th and 8th dpi with doses of 25, 12.5 or 6.25 mg/kg/day.…”

In Vitro Primary Screening of a Synthetic Series of Chromenoazoldiones against Trypanosoma cruzi

“…Quinones generate reactive oxygen species (ROS), which not only results in their antitumor properties, but also in a mechanism for designing antichagasic drugs. Here, a synthetic series of seven chromenoazoldiones previously defined as potential antitumorals [2,3], has been assayed in vitro against Trypanosoma cruzi (CL-B5 lacZ strain) in a primary screening that evaluates activity over epimastigotes and toxicity on L929 cells [4,5]. Compounds PM199, PM203 and PM401 achieved higher IC50 values than that of the reference drug benznidazole (BZ): IC50 = 14.45 ± 1.90, 14.84 ± 4.49, 16.01 ± 9.06 and 36.47 ± 4.43 µM (PM199, PM203, PM401 and BZ, respectively).…”