Progress has been made in the study of monoazole alkaloids

Monoterpene Indole Alkaloids (MIAs) is a hot topic in the study of natural pharmaceutical chemistry because of its diverse structure, abundant biological activity and high drug rate.
so far, about 3000 MIAs have been reported, including dozens of clinical drugs, such as Changchun alkali, magpie alkali, quinine, staphylaxis, rose tree alkali and so on.
Plant chemistry and western plant resources of Kunming Plant Research Institute of the Chinese Academy of Sciences continue to make use of the national key laboratory, Yunnan characteristic plant resources utilization and development team researcher Cai Xianghai research team has been committed to Yunnan characteristic plant resources INAS structure excavation and the exploration of new biological functions.
, the team has discovered several novel skeletons of MIAs (Organic Letters, 2019, 21, 4554; organic Letters, 2019, 21, 5938) and DMIAs with anti-tumor activity (Journal of Natural Products, 2017, 80, 790; Phytochemistry, 2018, 152, 125), and MIAs (Phytochemistry, 2019, 166, 50) with potential inhibition of jaundice oxidase activity were also found.
recently, Cai Xianghai's team made progress in the study of the biological function of the nervous system in the excavation of MIAs structural skeletons and in the study of non-cytoxic MIAs.
Jing, a Ph.D. student who was a member of the team, found a class of monomonyquine-type new skeleton alkaloid Meroyunnanines A, B, and C (Figure 1, Hot off the Press) in the study of the fruits of melodinus yunnanensis. Natural Product Reports, 2020, 22), compared to scandine, the main component in Yunnan mountain orange fruit, the new skeleton molecule forms a new carbon bond between C2 and C19, forming a caged six-ring system, the absolute configuration of which is determined by mr.
can be formed by tabersonine through oxidation re-discharge of two different pathways, respectively, such new compounds and scandine-type alkaloids.
In addition, through the screening test of neurotrophic activity of neurons cultured cortical neurons in in-body mice, it was found that the compound scandine N4-oxide promoted the growth of nerve protrusion at a concentration of 10 μM, indicating its potential neuropentration activity.
study was published on Organic Letters under the title Cage-Monoterpenoid Quinoline Alkaloids with Neurite Growth Growth Effects from the Fruits of Melodinus Yunnanensis. Small glial cells are immune cells of the central nervous system that continuously regulate the steady state of the central nervous system.
normal state, small glial cells have the role of participating in signaling, synhap repair, and immune supervision.
when stimulated (when chronic inflammation occurs in the central nervous system), the cell is activated in large numbers.
Small glial cells release inflammatory media and some neurotoxic substances of peroxides, leading to neural necrosis, and on the other hand, the removal of nerve cell debris through immunophagy facilitates their regeneration, while secreting their respective cytokines to promote damaged neuron repair.
, small glial cell activity plays a dual role in damage and repair to the central nervous system, and is closely related to chronic diseases such as Alzheimer's disease (AD), cerebral infarction and nerve pain.
inhibition of activated small glial cells is an important indicator in the neuroinflamed response and an important target for the discovery of pilot compounds.
Recently, dr. Yu Yang, a member of the team, obtained 12 dimiAs molecules of the same type (Figure 2) from the leaves of the medicinal dog tooth flower (Tabernamontana bovina), which are connected by a single bond of C-3 and C-14' from birchline and its derivatives.
In order to excavate and study the biological function of such molecules, the research team, in collaboration with Dr. Zhao Si of Shanghai University of Science and Technology, conducted an in vitro LPS-induced inhibitory activity screening experiment for small glial BV2 cell activation, and found that tabernaemontines G in such molecules had inhibited BV2 cell activation activity, and further studies showed that tabernaemontines G molecule inhibited BV2 cell activation by blocking P-38 signal activation.
study found that MIAs have biological functions to suppress neurological inflammation and are rare molecules in the natural pharmaceutical chemistry community to express such activity.
research, published on Organic Chemistry Frontiers, is based on the an Aspidosperma-type Alkaloid Dimer from Tabernamontana bovina As candidate for the Analytics of Microglial Activation.
isomer in the natural world, especially in steroids.
, however, MIAs are fixed configurations of their biomass preaphase tryptophan and rip-ring ma qianziline, which provide an important reference for determining MIAs bone architecture type through this source pathway.
studies have also found that individual alkaloids are present in isomer phenomena, such as (±) - voaphylline, (±) - eburnamine, and (±) - cleavamine (±) - coronaridine and (±) - vincadifformine, but the miAs above show isomers in different plants and even different genus, the existence of co-existence of MIAs is one of the important scientific issues in this class of alkaloids.
Dr. Yu Yang found two pairs of isomers (Figure 3) from the stems of medicinal dogs, and further speculated that the pair may have formed a key subamine salt intermediate by a series of oxidation fractures of the secodine prelude, which in turn formed a skeleton with multiple hand centers and multiple rings.
the detection of this complex alkaloid in the center of multi-handness is rare in nature, and the discovery of non-ethontho-proportional isomers is not easy (Figure 3), which is of great significance for the subsequent exploration of "pure" MIAs molecules.
research was published in China Journal of Chemistry under the title "Discovery of Natural Co-regulation Enantiomers of Monoterpenoid Indole Alkaloids."
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