Synthesis and in vitro antiprotozoal evaluation of novel metronidazole–Schiff base hybrids

Abstract

Herein we report the synthesis of 21 novel small molecules inspired by metronidazole and Schiff base compounds. The compounds were evaluated against Trichomonas vaginalis and cross-screened against other pathogenic protozoans of clinical relevance. Most of these compounds were potent against T. vaginalis, exhibiting IC 50 values < 5 µM. Compound 20, the most active compound against T. vaginalis, exhibited an IC 50 value of 3.4 µM. A few compounds also exhibited activity against Plasmodium falciparum and Trypanosomal brucei brucei, with compound 6 exhibiting an IC 50 value of 0.7 µM against P. falciparum and compound 22 exhibiting an IC 50 value of 1.4 µM against T.b. brucei. Compound 22 is a broad-spectrum antiprotozoal agent, showing activities against all three pathogenic protozoans under investigation.

Using 5-Nitroimidazole Derivatives against Neglected Tropical Protozoan Diseases: Systematic Review

“…The most potent compounds exhibited a similar activity to that of the control (CQ IC50 = 0.05 These compounds show IC50 values ranging from >20 μM to 0.7 μM (Table 4). The most potent compounds exhibited a similar activity to that of the control (CQ IC50 = 0.05 μM) [19].…”

“…In parallel, metronidazole (an antimicrobial agent with a nitroimidazole scaffold) has been used as a starting point for developing novel anti-malarial agents. In 2023, Beteck et al generated molecular hybrids with different Schiff bases, obtaining 21 new compounds (29 to 50) (Figure 7) [19]. These compounds show IC50 values ranging from >20 μM to 0.7 μM (Table 4).…”

“…Table 4. Activity of metronidazole-hybridized derivatives against chloroquine-susceptible P. falciparum strain (3D7) [19]. These compounds show IC50 values ranging from >20 μM to 0.7 μM (Table 4).…”

Tractable Quinolone Hydrazides Exhibiting Sub‐Micromolar and Broad Spectrum Antitrypanosomal Activities

“…The mixture was heated under reflux for 24–48 h. After completion (confirmed by TLC), the crude products were isolated by filtration then recrystallized from ethanol. This procedure afforded compounds 4 – 18 in a 30 to 70 % yield [39] …”

“…We have previously reported several compound classes exhibiting antitrypanosomal activity, [ 38 , 39 , 40 ] including quinolone-based compounds. [ 41 , 42 ] Our interest in quinolones is motivated by the tractability of this scaffold, and the fact that it can easily be modified at eight different positions to generate novel compounds with diverse biological and physico-chemical properties.…”