Recent Developments of Gramine: Chemistry and Biological Activity

Abstract

The natural alkaloid gramine has attracted significant attention in both academic and industrial circles because of its potential and diverse biological activities, including antiviral, antibacterial, antifungal, anti-inflammatory and antitumor activities; application in therapy for Alzheimer’s disease; serotonin-receptor-related activity; insecticidal activity; and application as an algicide. In this review, we focus on the research advances that have been made for gramine-based molecules since their discovery, providing key information on their extraction and separation, chemical synthesis and diverse biological activities. Data regarding their mechanisms of action are also presented. This comprehensive and critical review will serve as a guide for developing more drug candidates based on gramine skeletons.

Metabolic Activation and Cytotoxicity of Gramine Mediated by CYP3A in Rats

“…38,39 GRM, a natural alkaloid obtained from Gramineae plants, has a wide application for pest control and drug development. 40,41 The alkaloid has been reported to be extensively present in agricultural land and groundwater. 17,18 Acute mortality of domestic animals has occurred through consumption of plants containing this compound.…”

“…Plant-derived allelopathic compounds have become new generation pesticides, thereby reducing the environmental stress caused by synthetic chemicals. , As a result, the secondary metabolites produced by plants are widely distributed in aquatic environments and land. , Some are toxic and have harmful effects on organisms in the environment. , GRM, a natural alkaloid obtained from Gramineae plants, has a wide application for pest control and drug development. , The alkaloid has been reported to be extensively present in agricultural land and groundwater. , Acute mortality of domestic animals has occurred through consumption of plants containing this compound. , The resistance of GRM to degradation has a negative impact on human health. Elucidation of the mechanism of hepatotoxicity caused by exposure to GRM is of great significance.…”

Alkaloidal Extracts from Avicennia africana P. Beauv. (Avicenniaceae) Leaf: An Antiplasmodial, Antioxidant, and Erythrocyte Viable

“…Of the various compounds identified in the alkaloidal extract (AAA), gramine, a simple indole alkaloid, was found to have the highest percentage peak area of all the phytocompounds. Gramine has recently gained prominence due to its diverse biological activities, which include insecticidal, antibacterial, antiviral, antitumor, and anti-inflammatory properties [ 46 ]. It may be suggested that the antiplasmodial effects of the AAA extract in this study are largely due to the intrinsic indole alkaloids and isoquinoline alkaloids in the extract.…”

Cooperative Triple Catalysis Enables Deaminative α-Indolmethylation of Carbonyl Compounds with Gramines

“…Gramine, a natural indole alkaloid existing in higher plants, can be obtained by the Mannich reaction of indole . The classical Somei–Kametani reaction, which is widely used for the total synthesis of natural products, achieves the deaminative coupling of gramines with active carbon nucleophiles such as nitroalkanes, malonates, and cyanides in the presence of n -Bu 3 P as an activating reagent (Scheme a). , Later, ethyl propiolate and 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) were respectively reported as activating reagents for the deaminative coupling of gramines with active methylene carbon nucleophiles (Scheme b). , There were also sporadic reports on the deaminative coupling of gramines with sp 2 carbon nucleophiles (Scheme c) .…”