Antifilarial Activity of 1,3-Diarylpropen-1-One: Effect on Glutathione-S-Transferase, a Phase II Detoxification Enzyme

Abstract

Chalcone derivatives were evaluated for their antifilarial activity on Setaria cervi using glutathione-S-transferase (GST) as a drug target. The compounds 1-(4-benzotriazol-1-yl-phenyl)-3-(4-methoxyphenyl)prop-2-en-1-one (5), and 3-(4-methoxyphenyl)-1-(4-pyrrolidin-1-yl-phenyl) prop-2-en-1-one (7) showed a significant suppression (P < 0.01) in GST activity of adult female parasite extract at 3 microM concentration in vitro. However, GST activity was detected along with depletion in GSH level. Except Compounds 1 and 2, all exhibited a significant effect on the motility and viability of adult parasites. Compounds 3-(4-chlorophenyl)-1-(4-piperidin-1-yl-phenyl)prop-2-en-1-one (3), 1-(4-benzotriazol-1-yl-phenyl)-3-(4-methoxyphenyl)prop-2-en-1-one (5), and 3-(4-methoxyphenyl)-1-(4-pyrrolidin-1-yl-phenyl) prop-2-en-1-one (7) exhibited major irreversible effects on viability and resulted in parasite death and also inhibited the GST activity by 84-100% in vitro. We report for the first time the antifilarial activity of chalcones on GST of adult parasites. This study also strengthens our previous findings where GST is reported as a potential drug target for antifilarials.

Synthèse et criblage antiplasmodial de quelques benzimidazolyl-chalcones

“…Un début d'explication pourrait venir de leur possible spécificité d'action vis-à-vis des facteurs de résistances plutôt que ceux à l'origine de la sensibilité des plasmodies aux médicaments antipaludiques. L'on pourrait également s'orienter vers de possibles modes d'action de ces chalcones non pas sur des enzymes à fonction thiol (Awasthi et al, 2009) mais plutôt vers un possible mécanisme d'action par inhibition du fumarate réductase de P. falciparum comme c'est le cas avec la Licochalcone A (Fumika et al, 2005). Au final, la benzimidazolyl-chalcone 6e (CI 50 =5,63 µM), avait un meilleur profil antiplasmodial vis-à-vis de l'isolat de P. falciparum chloroquino-sensible.…”

Chalcone scaffolds as anti-infective agents: Structural and molecular target perspectives

“…SAR studies strongly support that small and medium-sized highly lipophilic or hydrophobic groups containing single or multiple nitrogen or oxygen in an acetophenone ring of chalcone have potent inhibitory effects on motility and GST activity of the parasite[122] (Figure 16). having a very bad repute for causing diseases, but in reality only a few are actually pathogenic in nature and evade host defenses, thereby causes infection all over the human structure, ranging from meninges (caused by Neisseria meningitidis) to foot (caused byStaphylococcus aureus).…”

Synthesis and antibacterial activity of novel fluoroquinolone analogs

“…Therefore, there is an urgent need to design and screened for antimicrobial activity. Our laboratory is working on design and synthesis of antimicrobial agents (Bhattacharya et al, 2009;Dixit et al, 2012;Yadav et al, 2012;Mishra et al, 2008;Awasthi et al, 2009) and X-ray crystal structure analysis (Singh et al, 2011) of small molecules. To diversify the work, we synthesized norfloxacin derivatives (5-22) and screened for their antibacterial activity.…”