Chloroquinoline–acetamide hybrids: a promising series of potential antiprotozoal agents

Abstract

In an endeavour to develop efficacious antiprotozoal agents 2-[4-(7-chloroquinolin-4-yl)piperazin-1yl]acetamide derivatives were synthesized and screened in vitro against the HM1:IMSS strain of E. histolytica and 3D7 strain of P. falciparum. Among the twenty-seven synthesized compounds, eleven evinced propitious anti-amoebic activity with IC50 values ranging from 0.41 to 1.80 µM) lower than the standard drug metronidazole (IC50 1.80 µM). All the compounds inhibited the in vitro growth of P. falciparum (IC50 range: 0.30-33.52 µM). Compounds A22 and A25 were found to be the most active antimalarial derivatives, and compound A16 the most active in inhibiting β-haematin formation; however compound A25 displayed the more favourable safety profile. The crystal structure for the compounds A7, A8, A12 and A21 was also determined. The molecular docking of crystal resolved inhibitors with PfDHFR allowed identification of stabilizing interactions within enzyme active site. These compounds affirm potential for further derivatives to enhance antiprotozoal activity whilst retaining their safety profile.

Parasitic diarrheal disease: drug development and targets

“…Metronidazole hydrazone conjugates were synthesized and screened in vitro for antiamoebic activity, the compound ( 18 ) was found more active (Ansari et al, 2015 ). A series of chloroquinoline-acetamide hybrids were synthesized and the compound ( 19 ) inhibit the growth of E. histolytica (Inam et al, 2015 ). The N -acylhydrazones derived from 7-chloro-4-piperazin-1-yl-quinoline were evaluated against E. histolytica and the compound ( 20 ) was more potent than metronidazole (Inam et al, 2014 ).…”

Design, synthesis, and pharmacological characterization of some 2‐substituted‐3‐phenyl‐quinazolin‐4(3H)‐one derivatives as phosphodiesterase inhibitors

“…Likewise, the targeted compounds 7a – e were obtained upon heating reactant 1 with the prepared aromatic chloroacetamides 6a – e [ 38–40 ] in dimethylformamide in the presence of potassium carbonate as a base catalyst. IR spectra of 7a – e expressed NH stretching bands in the range of 3341–3287 cm −1 and C═O stretching band for the aromatic acetamide derivatives in the range of 1663–1655 cm −1 .…”

“…Compounds 1 , [ 29,30 ] 2a – e , [ 31–36 ] 4a , b , [ 37 ] 6a – e , [ 38–40 ] and 8a – d [ 41 ] were prepared according to their reported procedures.…”

Structural and biological survey of 7‐chloro‐4‐(piperazin‐1‐yl)quinoline and its derivatives

“…Also, they reported a series of 2‐[4‐(7‐chloroquinolin‐4‐yl)piperazin‐1‐yl] acetamide derivatives ( 42 ). Most of the compounds exhibited higher activity as antiamoebic, IC 50 values of which ranges from 0.41 to 1.80 μM than Metronidazole “the reference compound” (IC 50 : 1.80 μM) (Inam et al, 2015). In 2015, Saleh et al reported compounds 43 and 44 , they exhibited great antigiardial (IC 50 : 4.3 and 2.9 μg/ml, respectively) compared with metronidazole (IC 50 : 7.3 μg/ml).…”