Leveraging off higher plant phylogenetic insights for antiplasmodial drug discovery

doi:10.1007/s13659-023-00396-x

应用天然产物 ›› 2023, Vol. 13 ›› Issue (5): 35-35.DOI: 10.1007/s13659-023-00396-x

Leveraging off higher plant phylogenetic insights for antiplasmodial drug discovery

Phanankosi Moyo¹, Luke Invernizzi¹, Sephora M. Mianda¹, Wiehan Rudolph¹, Warren A. Andayi², Mingxun Wang³, Neil R. Crouch^4,5, Vinesh J. Maharaj¹

1. Biodiscovery Center, Department of Chemistry, Faculty of Natural and Agricultural Sciences, University of Pretoria, Private Bag X 20, Hatfield, Pretoria, 0028, South Africa;
2. Department of Physical and Biological Sciences, Murang'a University of Technology, Murang'a, Kenya;
3. Computer Science and Engineering, University of California Riverside, 900 University Ave, Riverside, CA, 92521, USA;
4. Biodiversity Research and Monitoring Directorate, South African National Biodiversity Institute, Berea Road, P. O. Box 52099, Durban, 4007, South Africa;
5. School of Chemistry and Physics, University of KwaZulu-Natal, Durban, 4041, South Africa

收稿日期:2023-08-03 出版日期:2023-10-24 发布日期:2023-11-03
通讯作者: Vinesh J. Maharaj,E-mail:vinesh.maharaj@up.ac.za
基金资助:
Foundation L’Oréal (4500453975).

Leveraging off higher plant phylogenetic insights for antiplasmodial drug discovery

Phanankosi Moyo¹, Luke Invernizzi¹, Sephora M. Mianda¹, Wiehan Rudolph¹, Warren A. Andayi², Mingxun Wang³, Neil R. Crouch^4,5, Vinesh J. Maharaj¹

1. Biodiscovery Center, Department of Chemistry, Faculty of Natural and Agricultural Sciences, University of Pretoria, Private Bag X 20, Hatfield, Pretoria, 0028, South Africa;
2. Department of Physical and Biological Sciences, Murang'a University of Technology, Murang'a, Kenya;
3. Computer Science and Engineering, University of California Riverside, 900 University Ave, Riverside, CA, 92521, USA;
4. Biodiversity Research and Monitoring Directorate, South African National Biodiversity Institute, Berea Road, P. O. Box 52099, Durban, 4007, South Africa;
5. School of Chemistry and Physics, University of KwaZulu-Natal, Durban, 4041, South Africa

Received:2023-08-03 Online:2023-10-24 Published:2023-11-03
Contact: Vinesh J. Maharaj,E-mail:vinesh.maharaj@up.ac.za
Supported by:
Foundation L’Oréal (4500453975).

摘要/Abstract

摘要： The antimalarial drug-resistance conundrum which threatens to reverse the great strides taken to curb the malaria scourge warrants an urgent need to find novel chemical scaffolds to serve as templates for the development of new antimalarial drugs. Plants represent a viable alternative source for the discovery of unique potential antiplasmodial chemical scaffolds. To expedite the discovery of new antiplasmodial compounds from plants, the aim of this study was to use phylogenetic analysis to identify higher plant orders and families that can be rationally prioritised for antimalarial drug discovery. We queried the PubMed database for publications documenting antiplasmodial properties of natural compounds isolated from higher plants. Thereafter, we manually collated compounds reported along with plant species of origin and relevant pharmacological data. We systematically assigned antiplasmodial-associated plant species into recognised families and orders, and then computed the resistance index, selectivity index and physicochemical properties of the compounds from each taxonomic group. Correlating the generated phylogenetic trees and the biological data of each clade allowed for the identification of 3 ‘hot’ plant orders and families. The top 3 ranked plant orders were the (i) Caryophyllales, (ii) Buxales, and (iii) Chloranthales. The top 3 ranked plant families were the (i) Ancistrocladaceae, (ii) Simaroubaceae, and (iii) Buxaceae. The highly active natural compounds (IC₅₀≤1 μM) isolated from these plant orders and families are structurally unique to the ‘legacy’ antimalarial drugs. Our study was able to identify the most prolific taxa at order and family rank that we propose be prioritised in the search for potent, safe and drug-like antimalarial molecules.

关键词: Natural products, Plants, Phylogenetics, Malaria, Drug-resistance, ‘Hot’ plants

Abstract: The antimalarial drug-resistance conundrum which threatens to reverse the great strides taken to curb the malaria scourge warrants an urgent need to find novel chemical scaffolds to serve as templates for the development of new antimalarial drugs. Plants represent a viable alternative source for the discovery of unique potential antiplasmodial chemical scaffolds. To expedite the discovery of new antiplasmodial compounds from plants, the aim of this study was to use phylogenetic analysis to identify higher plant orders and families that can be rationally prioritised for antimalarial drug discovery. We queried the PubMed database for publications documenting antiplasmodial properties of natural compounds isolated from higher plants. Thereafter, we manually collated compounds reported along with plant species of origin and relevant pharmacological data. We systematically assigned antiplasmodial-associated plant species into recognised families and orders, and then computed the resistance index, selectivity index and physicochemical properties of the compounds from each taxonomic group. Correlating the generated phylogenetic trees and the biological data of each clade allowed for the identification of 3 ‘hot’ plant orders and families. The top 3 ranked plant orders were the (i) Caryophyllales, (ii) Buxales, and (iii) Chloranthales. The top 3 ranked plant families were the (i) Ancistrocladaceae, (ii) Simaroubaceae, and (iii) Buxaceae. The highly active natural compounds (IC₅₀≤1 μM) isolated from these plant orders and families are structurally unique to the ‘legacy’ antimalarial drugs. Our study was able to identify the most prolific taxa at order and family rank that we propose be prioritised in the search for potent, safe and drug-like antimalarial molecules.

Key words: Natural products, Plants, Phylogenetics, Malaria, Drug-resistance, ‘Hot’ plants

Phanankosi Moyo, Luke Invernizzi, Sephora M. Mianda, Wiehan Rudolph, Warren A. Andayi, Mingxun Wang, Neil R. Crouch, Vinesh J. Maharaj. Leveraging off higher plant phylogenetic insights for antiplasmodial drug discovery[J]. 应用天然产物, 2023, 13(5): 35-35.

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Leveraging off higher plant phylogenetic insights for antiplasmodial drug discovery

Leveraging off higher plant phylogenetic insights for antiplasmodial drug discovery

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