Evidence map›Paper›PMID 37821775›Full record

ArticleNatural products and bioprospecting2023

Prioritised identification of structural classes of natural products from higher plants in the expedition of antimalarial drug discovery.

Phanankosi Moyo, Luke Invernizzi, Sephora M Mianda, Wiehan Rudolph, Andrew W Andayi, Mingxun Wang, Neil R Crouch, Vinesh J Maharaj

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Natural products and bioprospecting, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Phanankosi MoyoDepartment of Chemistry, Faculty of Natural and Agricultural Sciences, Biodiscovery Center, University of Pretoria, Private Bag X 20, Hatfield, Pretoria, 0028, South Africa.ORCID http://orcid.org/0000-0001-7692-3256
Luke InvernizziDepartment of Chemistry, Faculty of Natural and Agricultural Sciences, Biodiscovery Center, University of Pretoria, Private Bag X 20, Hatfield, Pretoria, 0028, South Africa.ORCID http://orcid.org/0000-0003-1095-365X
Sephora M MiandaDepartment of Chemistry, Faculty of Natural and Agricultural Sciences, Biodiscovery Center, University of Pretoria, Private Bag X 20, Hatfield, Pretoria, 0028, South Africa.ORCID http://orcid.org/0000-0002-7586-4765
Wiehan RudolphDepartment of Chemistry, Faculty of Natural and Agricultural Sciences, Biodiscovery Center, University of Pretoria, Private Bag X 20, Hatfield, Pretoria, 0028, South Africa.ORCID http://orcid.org/0000-0001-7388-7966
Andrew W AndayiDepartment of Physical and Biological Sciences, Murang'a University of Technology Murang'a, Murang'a, Kenya.ORCID http://orcid.org/0000-0002-6331-7553
Mingxun WangComputer Science and Engineering, University of California Riverside, 900 University Ave, Riverside, CA, 92521, USA.ORCID http://orcid.org/0000-0001-7647-6097
Neil R CrouchBiodiversity Research and Monitoring Directorate, South African National Biodiversity Institute, Berea Road, P.O. Box 52099, Durban, 4007, South Africa.ORCID http://orcid.org/0000-0002-4938-5840
Vinesh J MaharajDepartment of Chemistry, Faculty of Natural and Agricultural Sciences, Biodiscovery Center, University of Pretoria, Private Bag X 20, Hatfield, Pretoria, 0028, South Africa. vinesh.maharaj@up.ac.za.ORCID http://orcid.org/0000-0002-6512-304X

Funding

Fondation L'Oréal 4500453975
6 · The paper itself

Abstract

The emergence and spread of drug-recalcitrant Plasmodium falciparum parasites threaten to reverse the gains made in the fight against malaria. Urgent measures need to be taken to curb this impending challenge. The higher plant-derived sesquiterpene, quinoline alkaloids, and naphthoquinone natural product classes of compounds have previously served as phenomenal chemical scaffolds from which integral antimalarial drugs were developed. Historical successes serve as an inspiration for the continued investigation of plant-derived natural products compounds in search of novel molecular templates from which new antimalarial drugs could be developed. The aim of this study was to identify potential chemical scaffolds for malaria drug discovery following analysis of historical data on phytochemicals screened in vitro against P. falciparum. To identify these novel scaffolds, we queried an in-house manually curated database of plant-derived natural product compounds and their in vitro biological data. Natural products were assigned to different structural classes using NPClassifier. To identify the most promising chemical scaffolds, we then correlated natural compound class with bioactivity and other data, namely (i) potency, (ii) resistance index, (iii) selectivity index and (iv) physicochemical properties. We used an unbiased scoring system to rank the different natural product classes based on the assessment of their bioactivity data. From this analysis we identified the top-ranked natural product pathway as the alkaloids. The top three ranked super classes identified were (i) pseudoalkaloids, (ii) naphthalenes and (iii) tyrosine alkaloids and the top five ranked classes (i) quassinoids (of super class triterpenoids), (ii) steroidal alkaloids (of super class pseudoalkaloids) (iii) cycloeudesmane sesquiterpenoids (of super class triterpenoids) (iv) isoquinoline alkaloids (of super class tyrosine alkaloids) and (v) naphthoquinones (of super class naphthalenes). Launched chemical space of these identified classes of compounds was, by and large, distinct from that of 'legacy' antimalarial drugs. Our study was able to identify chemical scaffolds with acceptable biological properties that are structurally different from current and previously used antimalarial drugs. These molecules have the potential to be developed into new antimalarial drugs.

Indexed as

Antiplasmodial drug resistanceCompound classesDrug developmentMalariaNatural productsPhytochemicalsPlasmodium falciparum

Identifiers

PMID37821775
PMCPMC10567616

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.