Abstract
Despite the vigorous research and development, as of 2017, there is currently no widely available antimalarial vaccine. An effective, commercially available vaccine would be a huge game changer; however, it seems like there is still a long way to go until that target is reached. Therefore, the purpose of this study was to use molecular docking technique to identify new inhibitors for a novel antimalarial target with the overall aim of finding hit compounds which could be further optimized to become potential drug candidates. The docking protocol AutoDockVina was used alongside the molecular visualisation software UCSF Chimera to dock 100 naphthoquinones (labelled TM1-100) and 66 aryl diketones (labelled TM101-166) with the chosen target, Plasmodium vivax N-myristoyltransferase (PvNMT). Each docking session yielded the best 9 binding modes between the ligand and target. The hydrogen bond interactions of all binding modes were analysed, and the top six target molecules (TM) were short listed as the possible hit compounds (TM40, TM65, TM66, TM81, TM94 and TM165). These compounds displayed more than six hydrogen bonds under 3 angstroms over the 9 binding modes. Using Lipinski’s rule of 5, the potential hit compounds were further analysed to determine the drug-likeness and all were found to obey the parameters. Following the same method used to dock the ligands, twelve FDA approved antimalarial drugs were also docked with PvNMT for comparison purposes. Apart from proguanil, the other eleven antimalarial drugs displayed fewer hydrogen bonds under 3 angstroms over the 9 binding modes compared to all six of the potential hit compounds. This study discovered six compounds which displayed stronger interactions with the target protein compared to majority of the FDA approved drugs. The results of this investigation gave us new molecules that could be further investigated for the designing of novel drug-like compounds for the treatment of Malaria.
Highlights
A total of 91 countries were considered malaria-endemic in 2016 which is 17 countries less than in the year 2000 [1]
This study discovered six compounds which displayed stronger interactions with the target protein compared to majority of the FDA approved drugs
The deduction can be made that these ligands have a lack of strong interactions with Plasmodium vivax N-myristoyltransferase (PvNMT)
Summary
A total of 91 countries were considered malaria-endemic in 2016 which is 17 countries less than in the year 2000 [1]. The number of fatal malaria cases has decreased by more than 40% since 2000 for all World Health Organisation (WHO) regions [2]. An estimated 216 million cases of malaria occurred globally in 2016 alone, including 445,000 fatal cases [1]. A substantial portion of these cases (194 million) were reported in the African region which has been the case for many years. The elderly and pregnant women are at most risk of contracting malaria [3]. This is evident as the majority of the fatal cases were reported to be children under the age of five [1]
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