Unveiling the anti-echinococcal efficacy of amide-based compounds: An in-silico and in-vitro study

Abstract

Cystic echinococcosis (CE) is a significant global public health concern, particularly in regions where livestock rearing is prevalent. Despite its impact on morbidity and mortality, CE has received insufficient attention compared to other neglected tropical diseases. The complexities in CE management arise from challenges in early detection, effective treatment, and parasite eradication. The present study addresses this gap by exploring innovative therapeutic approaches using amide-based compounds. In recent years, computational approaches and in-vitro studies have become prominent in neglected tropical disease drug discovery. Leveraging insights from previous studies on amide-based compounds with anti-parasitic potential, this study systematically designed, synthesized, and characterized a library of 30 amide compounds. The research integrated in-silico screening, molecular docking, and in-vitro experimentation to assess the anti-echinococcal potential of these compounds. The study identified five promising amide compounds, namely 3,5-dinitro-N-p-tolylbenzamide, N-p-tolyl-1-naphthamide, N-p-tolyl-4-(trifluoromethoxy)benzamide, 4-pentyl-N-p-tolylbenzamide, and 2,3,4,5,6-pentafluoro-N-p-tolylbenzamide, based on their docking scores. These compounds were synthesized and characterized through various spectroscopic techniques, confirming their structural integrity. The in-vitro cytotoxicity assay on HepG2 cell lines revealed varying degrees of cytotoxicity for the synthesized compounds. Notably, 4-pentyl-N-p-tolylbenzamide demonstrated the least cytotoxicity. Subsequent scolicidal activity assessments on E. granulosus protoscoleces demonstrated the potent protoscolicidal activity of N-p-tolyl-1-naphthamide, indicating its potential as an effective anti-echinococcal agent. Overall, this study presents a comprehensive exploration of amide-based compounds as potential therapeutic agents against CE. The findings contribute to the development of innovative strategies for CE treatment, addressing the urgent need for effective and safe drugs in managing this neglected tropical disease.