New peptide derived antimalaria and antimicrobial agents bearing sulphonamide moiety

D I Ugwuja,U C Okoro,S S Soman,R Soni,S N Okafor,D I Ugwu

doi:10.1080/14756366.2019.1651313

D I Ugwuja, U C Okoro + Show 4 more

Open Access

https://doi.org/10.1080/14756366.2019.1651313

Copy DOI

Abstract

Fourteen novel dipeptide carboxamide derivatives bearing benzensulphonamoyl propanamide were synthesized and characterized using 1H NMR, 13C NMR, FTIR and MS spectroscopic techniques. In vivo antimalarial and in vitro antimicrobial studies were carried out on these synthesized compounds. Molecular docking, haematological analysis, liver and kidney function tests were also evaluated to assess the effect of the compounds on the organs. At 200 mg/kg body weight, 7i inhibited the multiplication of the parasite by 81.38% on day 12 of post-treatment exposure. This was comparable to the 82.34% reduction with artemisinin. The minimum inhibitory concentration (MIC) in µM ranged from 0.03 to 2.34 with 7h having MIC of 0.03 µM against Plasmodium falciparium. The in vitro antibacterial activity of the compounds against some clinically isolated bacteria strains showed varied activities with some of the new compounds showing better activities against the bacteria and the fungi more than the reference drug ciprofloxacin and fluconazole.

Highlights

Malaria stands among one of the terrible diseases that have been known for more than 4000 years[1]
There are peptides that can be conjugated to a cargo to deliver it to a specific organ,[8] despite the advantages of the antimalaria peptide of having high target selectivity that reduces the usual side effects of small and low molecular weight drug, peptides mostly offer various challenges before it can be used as a therapeutic drug.[9]
We report the synthesis of short peptides containing sulfonamide and carboxamide functionalities with interesting antimalarial and antimicrobial activity

Summary

Introduction

Malaria stands among one of the terrible diseases that have been known for more than 4000 years[1]. Artemisinin and its combinational therapy is the most appropriate drug therapy for malaria in the malaria endemic region, but due to spread of artemisinin resistance in five countries, Cambodia, the Lao People’s Democratic Republic, Myanmar, Thailand and Viet Nam[3], urges the need for the development of new antimalaria. To this concern, lots of antimalaria and other therapeutic approaches are in the pipeline to impede the growth of this disease, including antimalaria peptides[4]. There are peptides (cell-penetrating as well as non-penetrating) that can be conjugated to a cargo to deliver it to a specific organ,[8] despite the advantages of the antimalaria peptide of having high target selectivity that reduces the usual side effects of small and low molecular weight drug, peptides mostly offer various challenges before it can be used as a therapeutic drug.[9]

Methods

Results

Conclusion