Unlocking nitrogen compounds’ promise against malaria: A comprehensive review

Plasmodium parasites are the primary cause of malaria, leading to high mortality rates, which require clinical attention. Many of the medications used in the treatment have resulted in resistance over time. Artemisinin combination therapy (ACT) has shown significant results for the treatment. Howeve...

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Published in:	Archiv der Pharmazie (Weinheim) Vol. 357; no. 9; pp. e2400222 - n/a
Main Authors:	Kuthe, Pranali Vijaykumar, Muzaffar‐Ur‐Rehman, Mohammad, Chandu, Ala, Prashant, Kirad Shivani, Sankarnarayanan, Murugesan
Format:	Journal Article
Language:	English
Published:	Germany Wiley Subscription Services, Inc 01-09-2024
Subjects:	Animals antimalarial agents Antimalarials - chemical synthesis Antimalarials - chemistry Antimalarials - pharmacology artemisinin combination therapy (ACT) Drug Discovery Drug Resistance Humans Malaria Malaria - drug therapy Malaria - parasitology Molecular Structure Nitrogen Compounds - chemical synthesis Nitrogen Compounds - chemistry Nitrogen Compounds - pharmacology nitrogen‐containing heterocycles Plasmodium Plasmodium - drug effects Structure-Activity Relationship nitrogen‐containing heterocycles Plasmodium artemisinin combination therapy (ACT) antimalarial agents malaria
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Summary:	Plasmodium parasites are the primary cause of malaria, leading to high mortality rates, which require clinical attention. Many of the medications used in the treatment have resulted in resistance over time. Artemisinin combination therapy (ACT) has shown significant results for the treatment. However, mutations in the parasite have resulted in resistance, leading to decreased efficiency of the medications that are currently being used. Therefore, there is a critical need to find novel scaffolds that are safe, effective, and of economic advantage. Literature has reported several potent molecules with diverse scaffolds designed, synthesized, and evaluated against different strains of Plasmodium. With this growing list of compounds, it is essential to collect the data in one place to gain a concise overview of the emerging scaffolds in recent years. For this purpose, nitrogen‐containing heterocycles such as β‐carboline, imidazole, quinazoline, quinoline, thiazole, and thiophene have been highly explored due to their wide biological applications. Besides these, another scaffold, benzodiazepine, which is majorly used as a central nervous system depressant, is emerging as an anti‐malarial agent. Hence, this review centers on the latest medication advancements designed to combat malaria, emphasizing special attention to 1,4‐benzodiazepines as a novel scaffold for antimalarial drug discovery. Many nitrogen‐containing heterocycles have been extensively investigated for their potential as antimalarial agents. Among the existing ones, 1,4‐benzodiazepine stands out as a relatively underexplored heterocyclic scaffold for the disease. This review reports the different substituents that can be incorporated into the privileged scaffold for antimalarial drug discovery.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 ObjectType-Review-3 content type line 23
ISSN:	0365-6233 1521-4184 1521-4184
DOI:	10.1002/ardp.202400222