AUTHOR=Mahmood Fawad , Jan Muhammad S. , Ahmad Sajjad , Rashid Umer , Ayaz Muhammad , Ullah Farhat , Hussain Fida , Ahmad Ashfaq , Khan Arif-ullah , Aasim Muhammad , Sadiq Abdul TITLE=Ethyl 3-oxo-2-(2,5-dioxopyrrolidin-3-yl)butanoate Derivatives: Anthelmintic and Cytotoxic Potentials, Antimicrobial, and Docking Studies JOURNAL=Frontiers in Chemistry VOLUME=5 YEAR=2017 URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2017.00119 DOI=10.3389/fchem.2017.00119 ISSN=2296-2646 ABSTRACT=

Development of multidrug resistance (MDR) to antimicrobial, antiparasitic and chemotherapeutic agents is a global challenge for the scientific community. Despite of the emergence of MDR pathogens, the development of novel and more effective drugs is slow and scientist even speculate that we are going back the pre-antibiotic era. This work aims to study and evaluate the preliminary antibacterial, anthelmintic and cytotoxic potentials of ethyl 3-oxo-2-(2,5-dioxopyrrolidin-3-yl)butanoates. Among all of the four compounds, compound 2 has displayed remarkable potency with MIC values of 0.125, 0.083, 0.073, and 0.109 mg/ml against E. sakazakii, E. coli. S. aureus, and K. pneumonia, respectively. Compared to etoposide (LC50 9.8 μg/ml), the compounds demonstrated LC50 values from 280 to 765 μg/ml. For anthelmintic assay, three concentrations of each compound and standard drug were studied in determination of time of death of the two species. Excellent anthelmintic activity was observed by all four compounds against P. posthuma and A. galli better than standard albendazole. High GOLD fitness score data from docking analysis toward the targets represent better protein–ligand binding affinity and thus indicate a high propensity for all the active compounds to bind to the active site. The promising in-vitro antimicrobial, anthelmintic activity, and cytotoxicity data conclusively revealed that these compounds may serve as viable lead compounds for the treatment of bacterial and parasitic infections, and therefore, could help the medicinal chemists to design future chemotherapeutic agents to avoid rapid drug resistance.