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

Natural Products and Bioprospecting

Original Article

Neil R. Crouch¹  Mingxun Wang²  Sephora M. Mianda³  Wiehan Rudolph³  Luke Invernizzi³  Phanankosi Moyo³  Vinesh J. Maharaj³  Andrew W. Andayi⁴ 

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

关键词: Natural products;    Compound classes;    Phytochemicals;    Plasmodium falciparum;    Antiplasmodial drug resistance;    Malaria;    Drug development;   

DOI  :  10.1007/s13659-023-00402-2

 received in 2023-08-03, accepted in 2023-10-01,  发布年份 2023

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© Kunming Institute of Botany, CAS 2023

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