Disruption of redox homeostasis with synchronized activation of apoptosis highlights the antifilarial efficacy of novel piperine derivatives: An in vitro mechanistic approach
| Autor: | Nikhilesh Joardar, Sudipto Saha, Satyajit Halder, Santi P. Sinha Babu, Pradip Shit, Utsab Debnath, Anup Kumar Misra, Kuladip Jana |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Polyunsaturated Alkamides Setaria Nematode Thioredoxin reductase Apoptosis Pharmacology Biochemistry 03 medical and health sciences chemistry.chemical_compound Alkaloids 0302 clinical medicine Piperidines Physiology (medical) Animals Homeostasis Benzodioxoles chemistry.chemical_classification Reactive oxygen species Redox homeostasis Chemistry In vitro 030104 developmental biology Enzyme Piperine Setaria cervi Cattle Oxidation-Reduction 030217 neurology & neurosurgery |
| Zdroj: | Free Radical Biology and Medicine. 169:343-360 |
| ISSN: | 0891-5849 |
| DOI: | 10.1016/j.freeradbiomed.2021.04.026 |
| Popis: | A series of novel piperine derivatives were synthesized with high yield and were evaluated for its antifilarial potential against the bovine filarial parasite Setaria cervi. Among 21 (3a-3u) compounds screened, three of them (3k, 3l, 3s) showed significant potential against all the developmental stages (oocytes, microfilariae and adult) of the filarial worm in time and dose dependent manner. 3l showed the highest efficacy among the selected three compounds. These three compounds were further evaluated for both in vitro and in vivo toxicity analyses which further fortified the benign nature of the selected compounds. The antifilarial activities they exhibited were clearly fuelled through disparity of the internal redox homeostasis as evidenced from the alterations in the enzymatic and non-enzymatic antioxidants level which ultimately shifted towards activation of pro-apoptotic signaling cascade eventually leading to the death of the parasites. The ability of the compound 3l to bind thioredoxin reductase and CED-3 protein are the key findings of this study. The present study supported with several biological experiments is therefore a maiden report on the antifilarial effectiveness of these novel piperine derivatives. |
| Databáze: | OpenAIRE |
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