Bioactive meroditerpenes and indole alkaloids from the soil fungus Neosartorya fischeri (KUFC 6344), and the marine-derived fungi Neosartorya laciniosa (KUFC 7896) and Neosartorya tsunodae (KUFC 9213)

Two new metabolites including a new aszonalenin analogue (1c) and a new meroditerpene (3) were isolated, together with aszonalenin (1a), acetylaszonalenin (1b), 13-oxofumitremorgin B (2), aszonapyrone A (4b) and helvolic acid, from the culture of the soil fungus Neosartorya fischeri (KUFC 6344). While the ethyl acetate extract of the culture of the diseased coral-derived fungus Neosartorya laciniosa (KUFC 7896) furnished aszonapyrone B (4a), aszonapyrone A (4b), tryptoquivaline L and 3′-(4-oxoquinazolin-3-yl) spiro[1H-indole-3,5′-oxolane]-2,2′-dione, the ethyl acetate extract of the culture of the marine sponge-associated fungus Neosartorya tsunodae (KUFC 9213) yielded a new analogue of chevalone C (5) and helvolic acid. The structures of the new compounds were established based on 1D and 2D NMR spectral analysis as well as HR-ESIMS. Compounds 1a–c, 2, 3, 4a, 4b and 5 were evaluated for their in vitro growth inhibitory activity on the MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer) and A375-C5 (melanoma) cell lines by the protein binding dye SRB method.     

Uncommon Terpenoids from Salvia Species: Chemistry,Biosynthesis and Biological Activities

The search for new bioactive compounds from plant sources has been and continues to be one of the most important fields of research in drug discovery. However, Natural Products research has continuously evolved, and more and more has gained a multidisciplinary character. Despite new developments of methodologies and concepts, one intriguing aspect still persists, i.e., different species belonging to the same genus can produce different secondary metabolites, whereas taxonomically different genera can produce the same compounds. The genus Salvia L. (Family Lamiaceae) comprises myriad distinct medicinal herbs used in traditional medicine worldwide that show different pharmacological activities due to the presence of a variety of interesting specialized metabolites, including mono-, sesqui-, di-, sester-, tri-, tetra-, and higher terpenoids as well as phenylpropanoids, phenolic acid derivatives, lignans, flavonoids, and alkaloids. We herein summarize the research progress on some uncommon terpenoids, isolated from members of the genus Salvia, which are well recognized for their potential pharmacological activities. This review also provides a current knowledge on the biosynthesis and occurrence of some interesting phytochemicals from Salvia species, viz. C₂₃-terpenoids, sesterterpenoids (C₂₅), dammarane triterpenoids (C₃₀), and uncommon triterpenoids (C₂₀+C₁₀). The study was carried out by searching various scientific databases, including Elsevier, ACS publications, Taylor and Francis, Wiley Online Library, MDPI, Springer, Thieme, and ProQuest. Therefore, 106 uncommon terpenoids were identified and summarized. Some of these compounds possessed a variety of pharmacological properties, such as antibacterial, antiviral, antiparasitic, cytotoxic and tubulin tyrosine ligase inhibitory activities. Due to the lack of pharmacological information for the presented compounds gathered from previous studies, biological investigation of these compounds should be reinvestigated.     

Sartorymensin,a new indole alkaloid,and new analogues of tryptoquivaline and fiscalins produced by Neosartorya siamensis (KUFC 6349)

Seven new indole alkaloids including a new indoloazepinone derivative (2), two new quinazolinone derivatives (7, 8) and four new pyrazinoquinazolinone derivatives: epi-fiscalin C (10), epi-fiscalin A (12), neofiscalin A (13), epi-neofiscalin A (14) were isolated, together with 4-dihydroxy-3-methylacetophenone (1), tryptoquivaline (3), tryptoquivalines L (4), H (5), F (6) as well as fiscalins A (11) and C (9), from the culture of the fungus Neosartorya siamensis (KUFC 6349). The absolute configuration of the stereogenic carbons of the previously reported tryptoquivalines F, H, L was revised using the data obtained from an X-ray analysis of tryptoquivaline l and the NOESY correlations. The structures of the new pyrazinoquinazolinone derivatives (10, 12, 13, 14) were established based on 1D and 2D NMR spectral analysis, and the absolute configuration of their stereogenic carbons was determined by an X-ray crystallographic analysis of fiscalin C (9) and a new compound epi-fiscalin C (10), in conjunction with the correlations observed in their NOESY and long range COSY spectra. Compounds 2–8 and 12 were evaluated for their in vitro growth inhibitory activity on the human U373 and Hs683 glioblastoma, the A549 non-small cell lung cancer, the MCF-7 breast cancer and the SKMEL-28 melanoma cell lines by MTT colorimetric assay.     

Effects of the Bark Resin Extract of Garcinia nigrolineata on Chronic Stress-Induced Memory Deficit in Mice Model and the In Vitro Monoamine Oxidases and β-Amyloid Aggregation Inhibitory Activities of Its Prenylated Xanthone Constituents

The present study describes investigation of the effects of the bark resin extract of Garcinia nigrolineata (Clusiaceae) on the cognitive function and the induction of oxidative stress in both frontal cortex and hippocampus by unpredictable chronic mild stress (UCMS). By using behavioral mouse models, i.e., the Y-maze test, the Novel Object Recognition Test (NORT), and the Morris Water Maze Test (MWMT), it was found that the negative impact of repeated mild stress-induced learning and memory deficit through brain oxidative stress in the UCMS mice was reversed by treatment with the bark resin extract G. nigrolineata. Moreover, the prenylated xanthones viz. cowagarcinone C, cowaxanthone, α-mangostin, cowaxanthone B, cowanin, fuscaxanthone A, fuscaxanthone B, xanthochymusxanthones A, 7-O-methylgarcinone E, and cowagarcinone A, isolated from the bark resin of G. nigrolineata, were assayed for their inhibitory activities against β-amyloid (Aβ) aggregation and monoamine oxidase enzymes (MAOs).     

Sartoryglabrins, analogs of ardeemins, from Neosartorya glabra

Chemical investigation of a collection of the fungus Neosartorya glabra from Thailand furnished sartoryglabins A-C (1a, 1b and 2) which are analogs of the reverse prenylated indole alkaloids known as (-) ardeemins. Structures of these compounds were established by NMR spectrometry and an X-ray analysis. Sartoryglabins A-C were evaluated for their in vitro growth inhibitory activity on three human tumor cell lines: MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer) and A375-C5 (melanoma). All the compounds exhibited strong to moderate activity against the MCF-7 cell line but weak or no activity against the NCI-H460 and A375-C5 cell lines. Sartoryglabin B was found to exhibit selectivity towards the MCF-7 cell line.     

Extension of Continuous Selection Sets to Non-Lipschitzian Quantum Stochastic Differential Inclusion

We establish results on multifunction associated with a set of solutions of non-Lipschitz quantum stochastic differential inclusion (QSDI), which still admits a continuous selection from some subsets of complex numbers. The results here generalize existing results.     

Improved methodologies for synthesis of prenylated xanthones by microwave irradiation and combination of heterogeneous catalysis (K10 clay) with microwave irradiation

Eleven prenylated xanthone derivatives (4-9, 11-15) have been synthesized for the first time by the microwave irradiation method. Prenylation of the xanthone building blocks 1 and 2 with prenyl bromide in alkaline medium, using microwave irradiation, gave the oxyprenylated xanthones 4 and 6, as major products in high yields, as well as diprenylated by-products (5, 7, 8, and 9) in very low yields. Microwave irradiation of oxyprenylated xanthones 4 and 6 furnished three new Claisen rearranged products (11, 14, and 15), as well as the previously described dihydrofuranoxanthones (12, 13). Furthermore, three new (19, 20, 21) and three previously described (16, 17, 18) dihydropyranoxanthones have also been prepared by a one-pot synthesis from xanthones 1, 2, and 3, using Montmorillonite K10 clay as a heterogeneous catalyst and a combination of Montmorillonite K10 clay with microwave irradiation in various conditions. The presence of solvent and the type of the clay (commercial or dry) were found to have a strong influence on the product yields. This is the first report of using these methodologies for the synthesis of dihydropyranoxanthone derivatives. The structures of the prenylated xanthones obtained were established by IR, UV, HRMS, and NMR (¹H, ¹³C, HSQC, and HMBC) techniques.     

Determination of the Absolute Configuration of Bioactive Indole-Containing Pyrazino[2,1-b]quinazoline-3,6-diones and Study of Their In Vitro Metabolic Profile

In recent decades, fungi-derived naturally occurring quinazolines have emerged as potential drug candidates. Nevertheless, most studies are conducted for bioactivity assays, and little is known about their absorption, distribution, metabolism, and elimination (ADME) properties. To perform metabolic studies, the synthesis of the naturally occurring quinazolinone, fiscalin B (1), and its chloro derivative, 4-((1H-indol-3-yl)methyl)-8,10-dichloro-1-isobutyl-1,2-dihydro-6H-pyrazino[2,1-b]quinazoline-3,6(4H)-dione (2), disclosed as an antibacterial agent, was performed in a gram scale using a microwave-assisted polycondensation reaction with 22% and 17% yields, respectively. The structure of the non-natural (+)-fiscalin B was established, for the first time, by X-ray crystallography as (1R,4S)-1, and the absolute configuration of the naturally occurring fiscalin B (-)-1 was confirmed by comparison of its calculated and experimental electronic circular dichroism (ECD) spectra as (1S,4R)-1. in vitro metabolic studies were monitored for this class of natural products for the first time by ultra-high-performance liquid chromatography (UHPLC) coupled with high-resolution mass spectrometry (HRMS). The metabolic characteristics of 1 and 2 in human liver microsomes indicated hydration and hydroxylation mass changes introduced to the parent drugs.     

Antidementia Effects of Alternanthera philoxeroides in Ovariectomized Mice Supported by NMR-Based Metabolomic Analysis

The crude ethanol extract of the whole plant of Alternanthera philoxeroides (Mart.) Griseb was investigated for its potential as antidementia, induced by estrogen deprivation, based on in vitro antioxidant activity, β-amyloid aggregation inhibition and cholinesterase inhibitory activity, as well as in vivo Morris water maze task (MWMT), novel object recognition task (NORT), and Y-maze task. To better understand the effect of the extract, oxidative stress-induced brain membrane damage through lipid peroxidation in the whole brain was also investigated. Additionally, expressions of neuroinflammatory cytokines (IL-1β, IL-6 and TNF-α) and estrogen receptor-mediated facilitation genes such as PI3K and AKT mRNA in the hippocampus and frontal cortex were also evaluated. These effects were confirmed by the determination of its serum metabolites by NMR metabolomic analysis. Both the crude extract of A. philoxeroides and its flavone constituents were found to inhibit β-amyloid (Aβ) aggregation.