Current scenario and future strategies to fight artemisinin resistance

Pasupureddy, Rahul; Atul, Atul; Seshadri, Sriram; Pande, Veena; Dixit, Rajnikant; Pandey, Kailash C.

doi:10.1007/s00436-018-6126-x

Cited by 13 publications

(6 citation statements)

References 143 publications

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“…2 The drug resistance of malaria parasite has led to the need and search for new chemical scaffolds that have novel modes of action and can act through new protein targets. 3,4 One of such protein targets in P falciparum is the adenylosuccinate lyase (ADSL), which is an important enzyme in purine metabolism. 5 The de novo purine biosynthetic pathway that gives rise to the formation of adenosine monophosphate (AMP), catalysed by ADSL, is absent in P falciparum , making it a potential drug target for antimalarial studies.…”

Section: Introductionmentioning

confidence: 99%

Homology Modelling and Molecular Docking Studies of Selected Substituted Benzo[d]imidazol-1-yl)methyl)benzimidamide Scaffolds on Plasmodium falciparum Adenylosuccinate Lyase Receptor

Oduselu

Ajani

Ajamma

et al. 2019

Bioinform Biol Insights

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Plasmodium falciparum adenylosuccinate lyase ( PfADSL) is an important enzyme in purine metabolism. Although several benzimidazole derivatives have been commercially developed into drugs, the template design as inhibitor against PfADSL has not been fully explored. This study aims to model the 3-dimensional (3D) structure of PfADSL, design and predict in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) of 8 substituted benzo[ d]imidazol-1-yl)methyl)benzimidamide compounds as well as predict the potential interaction modes and binding affinities of the designed ligands with the modelled PfADSL. PfADSL 3D structure was modelled using SWISS-MODEL, whereas the compounds were designed using ChemDraw Professional. ADMET predictions were done using OSIRIS Property Explorer and Swiss ADME, whereas molecular docking was done with AutoDock Tools. All designed compounds exhibited good in silico ADMET properties, hence can be considered safe for drug development. Binding energies ranged from −6.85 to −8.75 kcal/mol. Thus, they could be further synthesised and developed into active commercial antimalarial drugs.

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Section: Introductionmentioning

confidence: 99%

Homology Modelling and Molecular Docking Studies of Selected Substituted Benzo[d]imidazol-1-yl)methyl)benzimidamide Scaffolds on Plasmodium falciparum Adenylosuccinate Lyase Receptor

Oduselu

Ajani

Ajamma

et al. 2019

Bioinform Biol Insights

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“…Also, inhibitors targeting a specific protein/ligand could potentially inhibit parasite growth only in stages when the target proteins are expressed. Broad spectrum antimalarials, such as the current frontline drugs artemisinins (ARTs) and their combination therapies (ACTs), target and break down various cellular pathways including but not limited to hemozoin formation, DNA repair, and mitochondria machinery, which make them highly potent within short exposure times [10,11]. However, exposure to various cellular targets leads to the rapid development of drug resistance.…”

Section: Ppis In Malariamentioning

confidence: 99%

Protein-Protein Interactions in Malaria: Emerging Arena for Future Chemotherapeutics

Pasupureddy¹,

Seshadri²,

Dixit³

et al. 2020

Parasitology and Microbiology Research

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Malaria is one of the most deadly diseases infecting humans. Advances in elimination and vector control have reduced the global malaria burden in the past decade; however, the emerging threat of drug resistance and suboptimal vaccine efficacies threaten global eradication efforts. Unlocking novel drug and vaccine targets while simultaneously mitigating spread of resistant strains seems to be the need of the hour. Protein-protein interactions (PPIs), an integral part of hostpathogen cross-talk and parasite survival, have only recently emerged as promising drug targets. Large PPI networks (interactome) are being developed to better our understanding of various parasite biochemical pathways. In this chapter, we throw light on several newly characterized protein-protein interactions between the host (humans) and parasite (plasmodium) in key processes such as hemoglobin degradation, enzyme regulation, protein export, egress, invasion, and drug resistance and further discuss their viability for development as novel chemotherapeutic targets.

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“…This disease still becomes a significant challenge in the public health sector and drug resistance. Artemisinin and derivatives, which is known as the core treatment, are reported to develop resistance and spread over in Southeast Asia [25]- [27]. Artemisinin resistance can be defined as the delay in parasite clearance, which may cause the clinical failure of treatment [28], [29].…”

Section: Introductionmentioning

confidence: 99%

Using Phylogeny Approach on Ethnobotanical Bioprospecting for Leading Antimalarial Plant-Based Drug Discovery

Liana¹,

Rungsihirunrat²

2021

Int. J. Adv. Sci. Eng. Inf. Technol.

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Ethnobotanical-directed bioprospecting has made a significant contribution to modern drug discoveries. However, merely relying on this approach may spend more expenditure, time-consuming, and lead exhaustive laboratory testing due to the tremendous data of medicinal plants used and the occurrence of placebo effect during traditional medical treatment. Combining the phylogeny approach with ethnobotanical bioprospecting may become new prospective tools to lead the plant-based drug discovery, including antimalaria. This study aimed to map the ethnomedicinal plants used by various indigenous cultures to investigate the clustered pattern of its antimalarial properties for future bioprospecting. The Internal Transcribed Spacer (ITS) region sequences of selected 280 medicinal plants taxa obtained from NCBI (National Center for Biotechnology Information) were aligned by MUSCLE multiple sequences alignments. They were further analyzed using the Maximum Likelihood Phylogenetic Test by MEGA X software to construct the phylogenetic tree. Our research revealed that the medicinal plant taxa for malaria treatment was clumped in several families, including Apocynaceae, Euphorbiaceae, Rubiaceae, Rutaceae, Fabaceae were strongly clumped along with plants used for fever in the Asteraceae family. Interestingly, our finding showed that these plants were clumped in the sub-family of antimalarial producing species, the Asteroidea. Furthermore, the strongly clumping pattern was also shown in the tribe Heliantheae alliance of this sub-family. This finding supports the predictive power of phylogeny for future bioprospecting to select the candidate taxa to lead the drug discovery.

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Current scenario and future strategies to fight artemisinin resistance

Cited by 13 publications

References 143 publications

Homology Modelling and Molecular Docking Studies of Selected Substituted Benzo[d]imidazol-1-yl)methyl)benzimidamide Scaffolds on Plasmodium falciparum Adenylosuccinate Lyase Receptor

Homology Modelling and Molecular Docking Studies of Selected Substituted Benzo[d]imidazol-1-yl)methyl)benzimidamide Scaffolds on Plasmodium falciparum Adenylosuccinate Lyase Receptor

Protein-Protein Interactions in Malaria: Emerging Arena for Future Chemotherapeutics

Using Phylogeny Approach on Ethnobotanical Bioprospecting for Leading Antimalarial Plant-Based Drug Discovery

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