Stelleroids A-C, Three Rearranged Guaiane Sesquiterpenoids with Caged Ring Systems from .

Three highly modified sesquiterpenoids, stelleroids A-C (-, respectively), were isolated from the roots of . Biosynthetically, these molecules are derived from the 5/7-fused bicyclic guaiane, involving a series of skeletal rearrangements, leading to the formation of an adamantane-like 12-oxa-tetracyclo[6.2.

Fissistonones A and B: Two Phenylpropanoyl Prenylated Naphthoquinones with Rearranged Carbon Skeletons from .

Fissistonones A and B ( and ), two naphthoquinone derivatives with rearranged carbon skeletons, were obtained from the leaves of . Structurally, compounds and featured an unprecedented phenylpropanoyl benzobicyclo[3.3.

Acronynoids A-G, novel prenylated acetophenone-based meroterpenoids with angiogenesis inhibitory activities from Acronychia pedunculata.

Seven novel prenylated acetophenone-based meroterpenoids with new carbon skeletons, acronynoids A-G (1-7), were isolated from Acronychia pedunculata. These compounds represent the first examples of bis-prenylated acetophenone-sesquiterpenoid adducts, in which 1 featured a unique 6/6/6/9/4 fused pentacyclic ring system. Their structures with absolute configurations were established by extensive spectroscopic analyses and quantum-chemical calculations.

Design, Synthesis and Bioactive Evaluation of Topo I/ Dual Inhibitors to Inhibit Oral Cancer via Regulating the PI3K/AKT/NF-κB Signaling Pathway.

The significantly rising incidence of oral cancer worldwide urgently requires the identification of novel, effective molecular targets to inhibit the progression of malignancy. DNA topoisomerase I (Topo I) is a well-established target for cancer treatment, and many studies have shown that different cancer cell genes could be targeted more selectively with one type of Topo I inhibitor. In this report, a new scaffold pyridothieno[3,2-]isoquinoline 11,11-dioxide was designed via the combination of the key fragment or bioisoster of Topo I inhibitor azaindenoisoquinolines and G-quadruplex binder quindoline.

Copper-Catalyzed Enantioselective Skeletal Editing through a Formal Nitrogen Insertion into Indoles to Synthesize Atropisomeric Aminoaryl Quinoxalines.

Skeletal editing represents an attractive strategy for adding complexity to a given molecular scaffold in chemical synthesis. Isodesmic reactions provide a complementary skeletal editing approach for the redistribution of chemical bonds in chemical synthesis. However, catalytic enantioselective isodesmic reaction is extremely scarce and enantioselective isodesmic reaction to synthesize atropisomeric compounds is unknown.

Identification of O-arylated huperzinines as novel cholinergic anti-inflammatory pathway agonists against gout arthritis.

Lycodine alkaloids are important natural products with diverse biological effects. In this manuscript, we set out the first structural optimization of the 2-pyridone moiety of Lycodine alkaloid via selective O-arylation under metal-free conditions and obtained a series of potent bioactive molecules against monosodium urate (MSU)-induced IL-1β production. Further investigations demonstrated that these natural product derivatives could activate the neuro-immunomodulatory cholinergic anti-inflammatory pathway (CAP) to block the initial phase of NLRP3 inflammasome activation.

Synthesis of Indole-Fused Pyrazino[1,2-a]quinazolinones by Copper(I)-Catalyzed Selective Hydroamination-Cyclization of Alkynyl-tethered Quinazolinones.

We described a copper(I)-catalyzed atom economic and selective hydroamination-cyclization of alkynyl-tethered quinazolinones to prepare a variety of indole-fused pyrazino[1,2-a]quinazolinones in good to excellent yields ranging from 39 %-99 % under mild reaction conditions. Control experiments revealed that coordination-directed method of quinazolinone moiety with copper(I) was important for the selective hydroamination-cyclization of alkynes at the N1-atom instead of N3-atom of quinazolinone. The reaction could be easily performed at gram scales and some prepared indole-fused pyrazino[1,2-a]quinazolinones with donating groups on the indole moiety showed a distinct fluorescence emission wavelength with blue shift under the acid conditions.

Osthole Activates the Cholinergic Anti-Inflammatory Pathway via α7nAChR Upregulation to Alleviate Inflammatory Responses.

Osthole (also known as Osthol) is the main anti-inflammatory coumarin found in Cnidium monnieri and severs as the exclusive quality-controlled component according the Chinese Pharmacopoeia. However, its underlying anti-inflammatory mechanism remains unknown. In this study, we demonstrated that Osthole treatment significantly inhibited the generation of TNF-α, but not IL-6 in the classical LPS-stimulated RAW264.

Synthesis of 4-(trichloromethyl)pyrido[2',1':3,4]pyrazino[2,1-]quinazolinones through a cyclized dearomatization and trichloromethylation cascade strategy.

A variety of 4-(trichloromethyl)pyrido[2',1':3,4]pyrazino[2,1-]quinazolinones were prepared in moderate to good yields with high regioselectivity through intramolecular 6- cyclization and trichloromethylation of 3-alkynyl-2-pyridinyl-tethered quinazolinones in chloroform. Mechanistic studies revealed that chloroform might serve as a trichloromethyl anion precursor. Furthermore, the reaction could be easily performed on gram scales and an estrone-derived 4-(trichloromethyl)pyrido[2',1':3,4]pyrazino[2,1-]quinazolinone was prepared over five steps.

Design and synthesis of luotonin A-derived topoisomerase targeting scaffold with potent antitumor effect and low genotoxicity.

Conventional topoisomerase (Topo) inhibitors typically usually exert their cytotoxicity by damaging the DNAs, which exhibit high toxicity and tend to result in secondary carcinogenesis risk. Molecules that have potent topoisomerase inhibitory activity but involve less DNA damage provide more desirable scaffolds for developing novel chemotherapeutic agents. In this work, we broke the rigid pentacyclic system of luotonin A and synthesized thirty-three compounds as potential Topo inhibitors based on the devised molecular motif.

Diterpenoids from with Kv1.3 Inhibitory Activity.

diterpenoids possess inhibitory effects of Kv1.3 ion channel, but most of this research has focused on diterpenoids with jatrophane-related or ingenane-related skeletons. In the present study, nine undescribed (-) and 16 known (-) diterpenoids, based on jatrophane, lathyrane, ingenane, abietane, and atisane skeletons, were identified from the methanol extract of the aerial parts of .

Design and synthesis of pseudo-rutaecarpines as potent anti-inflammatory agents via regulating MAPK/NF-κB pathways to relieve inflammation-induced acute liver injury in mice.

Pseudo-natural products (PNPs) design strategy provides a great valuable entrance to effectively identify of novel bioactive scaffolds. In this report, novel pseudo-rutaecarpines were designed via the combination of several privileged structure units and 46 target compounds were synthesized. Most of them display moderate to potent inhibitory effect on LPS-induced NO production and low cytotoxicity in RAW264.

Anti-inflammatory lanostane triterpenoids with rearranged spirobi[indene] scaffold and their biogenetically related analogues from Euphorbia maculata.

Phytochemical investigations on the ethanol extract of the whole plant of Euphorbia maculata Linn. Resulted in the identification of 16 lanostane-related triterpenoids, including 11 undescribed ones, namely spiromaculatols A-C (1-3) and euphomaculatoids A-H (4-11). The structural determinations of the previously undescribed ones (1-11) were elucidated based on the interpretation of comprehensive spectroscopic data, quantum chemical calculation, as well as X-ray crystallographic experiments.

Acronyrones A-C, unusual prenylated acetophenones from Acronychia pedunculata.

Two novel prenylated acetophenones with new carbon skeletons, acronyrones A and B (1 and 2), and a new analogue, acronyrone C (3), together with two known compounds (4 and 5) were isolated from the leaves of Acronychia pedunculata. Their structures with absolute configurations were identified by interpretation of spectroscopic data, single crystal X-ray diffraction, and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 represent the first example of prenylated acetophenones possessed a C (1) and a C (2) side chain, forming a 4-isobutylchroman-2-one unit and a 3-(2-methylpropylidene)benzofuran-2(3H)-one moiety with the acetophenone core, respectively.

Brujavanoids A-U, structurally diverse apotirucallane-type triterpenoids from Brucea javanica and their anti-inflammatory effects.

Extensive phytochemical investigation on the methanol extract of the inflorescences, twigs, and leaves of Brucea javanica led to the isolation and identification of 27 triterpenoids, including 21 previously undescribed ones, named brujavanoids A-U (1-21). Their structures were determined based on comprehensive spectroscopic analysis and single-crystal X-ray diffraction. Of these compounds, brujavanoid A (1) represents the first apotirucallane-type triterpenoid with a novel 19(10 → 9)abeo motif, and brujavanoids B and C (2-3) are the first apotirucallane-type triterpenoids with a rarely occurring 14-hydorxy-15,16-epoxy fragment.

Structurally diverse steroids from an endophyte of Aspergillus tennesseensis 1022LEF attenuates LPS-induced inflammatory response through the cholinergic anti-inflammatory pathway.

The emerging cholinergic anti-inflammatory pathway plays a key role in regulating inflammation. Steroids are known to possess remarkable anti-inflammatory activity. However, the links between steroids and the cholinergic anti-inflammatory pathway remain unidentified.

Targeting a cryptic allosteric site of SIRT6 with small-molecule inhibitors that inhibit the migration of pancreatic cancer cells.

SIRT6 belongs to the conserved NAD-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD.

Jatrophane Diterpenoids with Kv1.3 Ion Channel Inhibitory Effects from .

Chemical investigation of bioactive components from the whole plant of resulted in the isolation and identification of 17 new jatrophane diterpenoids, namely, heliojatrone D () and helioscopids A-P (-), along with 11 known analogues (-). The structural elucidation of the new diterpenoids was achieved by the comprehensive analysis of HRESIMS, NMR, and X-ray crystallographic data, as well as using electronic circular dichroism. Structurally, heliojatone D () is the fourth natural diterpenoid with a rare bicyclo[8.

Diterpenoids with Rearranged 9(10→11)--10,12-Cyclojatrophane Skeleton and the First (15)-Jatrophane from : Structural Elucidation, Biomimetic Conversion, and Their Immunosuppressive Effects.

Two novel diterpenoids, one with a rearranged ,-fused tricyclo[10.3.0.

Probing Indole Diketopiperazine-Based Hybrids as Environmental-Induced Products from sp. EGF 15-0-3.

Comprehensive analyses of the metabolite spectra of sp. EGF 15-0-3 under different culture conditions revealed the presence of unique environmental-induced metabolites exclusively from the rice medium. Subsequent target isolation afforded four unprecedented indole diketopiperazine-based hybrids with a pyrano[3',2':7,8]isochromeno[4,3-]pyrazino[2,1-]indole core ( and ) or a spiro[piperazine-2,2'-pyrano[3,4,5-]chromene] scaffold ( and ).

Stelleranoids A-M, guaiane-type sesquiterpenoids based on [5,7] bicyclic system from Stellera chamaejasme and their cytotoxic activity.

Thirteen previously undescribed guaiane-type sesquiterpenoids based on [5,7] bicyclic system, stelleranoids A-M (1-13), along with six known analogues (14-20), were isolated from the roots of Stellera chamaejasme with chromatographic techniques. Their structures including absolute configurations were determined by HRESIMS and spectroscopic data, quantum chemical calculations, as well as X-ray crystallographic analysis. Cytotoxicity test in three cell lines indicated that compound 14 had relatively stronger cytotoxic effect against MKN-45, SKOV3, and Du145 cell lines with IC of 9.

Phloroglucinol-derived lipids from the leaves of Syzygium cumini and their neuroprotective activities.

Based on the typical HPLC-UV-MS profiles and characteristic H NMR signals, twelve new phloroglucinol-derived lipids (1-12), featuring a long linear aliphatic side chain, together with three known ones (13-15) were isolated from the ethanol extract of the leaves of Syzygium cumini. Their structures were elucidated on the basis of extensive NMR spectroscopic analyses and mass spectrometric data. Compounds 1-5 characterize an enolizable β,β'-tricarbonyl motif with a cyclohexa-3,5-dien-1-one core that is hitherto undescribed in phloroglucinol-derived lipids.

Rhodomentosones A and B: Two Pairs of Enantiomeric Phloroglucinol Trimers from and Their Asymmetric Biomimetic Synthesis.

Rhodomentosones A and B ( and ), two pairs of novel enantiomeric phloroglucinol trimers featuring a unique 6/5/5/6/5/5/6-fused ring system were isolated from . Their structures with absolute configurations were elucidated by NMR spectroscopy, X-ray crystallography, and ECD calculation. The bioinspired syntheses of and were achieved in six steps featuring an organocatalytic asymmetric dehydroxylation/Michael addition/Kornblum-DeLaMare rearrangement/ketalization cascade reaction.

Structurally diverse alkaloids from Buxus sempervirens with cardioprotective activity.

Extensive phytochemical study of the methanol extract of twigs and leaves of Buxus sempervirens resulted in the identification of 17 Buxus alkaloids, including 12 new ones, namely buxusemines A-L (1-12). Their structures were delineated by detailed analysis of the HRESIMS and NMR data, as well as quantum chemical NMR calculations. Buxusemine A (1) represents the second Buxus alkaloid with a unique spiro[4.

Modified Fusicoccane-Type Diterpenoids from .

Seven new modified fusicoccane-type diterpenoids (-), together with two known congeners ( and ), were obtained from . Their structures were elucidated from a combination of NMR and HRESIMS data and C NMR calculation as well as DP4+ probability analyses, and the absolute configurations of - were determined by ECD calculation and single-crystal X-ray diffraction (Cu Kα). Compounds - belong to a rare class of 16--dicyclopenta[]cyclooctane diterpenoids, and compounds and represent the first examples of fusicoccane-type diterpenoids featuring two previously undescribed tetracyclic 5/6/6/5 ring systems, while compound features a previously undescribed tetracyclic 5/8/5/3 ring system.