Five undescribed cyclopeptides from Cordyceps militaris.

Ustiloxins I-M (1-5), five undescribed cyclopeptides bearing a 15-membered macrocyclic skeleton, were isolated from Cordyceps militaris. The structures of 1 and 5 were identified by spectroscopic and crystallographic methods, whereas the structures of 2-4 were assigned by spectroscopic and computational approaches. Biological evaluation of all the compounds toward human triple-negative breast cancer cells revealed that compounds 4 and 5 are toxic with IC50 values of 64.29 µM and 28.89 µM, respectively.

Structurally Diverse Alkaloids with Anti-Renal-Fibrosis Activity from the Centipede Scolopendra subspinipes mutilans.

Twelve new alkaloids, scolopenolines A-L (1-7, 9-11, 13, 14), along with six known analogues, were isolated from Scolopendra subspinipes mutilans, identified by analysis of spectroscopic data and quantum chemical and computational methods. Scolopenoline A (1), a unique guanidyl-containing C14 quinoline alkaloid, features a 6/6/5 ring backbone. Scolopenoline B (2) is a novel sulfonyl-containing heterodimer comprising quinoline and tyramine moieties. Scolopenoline G (7) presents a rare C12 quinoline skeleton with a 6/6/5 ring system. Alkaloids 1, 8, 10, and 15-18 display anti-inflammatory activity, while 10 and 16-18 also exhibit anti-renal-fibrosis activity. Drug affinity responsive target stability and RNA-interference assays show that Lamp2 might be a potentially important target protein of 16 for anti-renal-fibrosis activity.

Structurally diverse phthalides from fibrous roots of Ligusticum chuanxiong Hort. and their biological activities.

Falonolide A (1) and B (2), two novel polyyne hybrid phthalides resulting from unprecedented carbon skeleton polymerized by Z-ligustilide and falcarindiol, along with six new related phthalides (3-8), were isolated from Ligusticum chuanxiong Hort. Their structures were elucidated by spectroscopic analysis, computer-assisted structure elucidation (CASE) analysis, DP4+ probability analysis and electronic circular dichroism (ECD) calculations. A plausible biosynthetic pathway for 1-8 was proposed, and the production mechanism of 2 was revealed by density functional theory (DFT) method. Compounds 4 and 6 exhibited significant vasodilatory activity with EC50 of 8.00 ± 0.86 and 6.92 ± 1.02 µM, respectively. Compound 4 also displayed significant inhibitory effect of NO production with EC50 value of 8.82 ± 0.30 µM. Based on the established compounds library, structure-activity relationship analysis of phthalides was explored to provide insights into the drug development of vasodilators and anti-flammatory.

Aspongopyrimidine A, a N-Peralkylated Histidine Zwitterion from Aspongopus chinensis against Alzheimer's Disease Targeting MAPRE3.

Aspongopyrimidine A (1), a hexa-1,3-diene-histidine-hexanoic acid adduct featuring a 4,5-dihydro-2H-10λ4-imidazo[5,1-f]pyrrolo[2,1-b]pyrimidine motif, was isolated from the insect Aspongopus chinensis. The structure was clarified by spectroscopic and computational methods and X-ray diffraction. Peralkylation of N-atoms in histidine by two C6 units makes 1 an inner salt with a 5/6/5 tricyclic system. Biological evaluation found that 1 exerts activity against Alzheimer's disease targeting MAPRE3 through a chemical proteomics approach. This study revealed unusual modifications of amino acids as the fundamental units of protein.

Isolation and target identification of anti-renal fibrosis compounds from Cordyceps militaris.

Four undescribed compounds including one aromatic glucoside derivative, cordyceglycoside A (1), one new isoleucine derivative inner salt, cordycepisosalt A (2), a rare four-membered lactam, cinerealactam B (3), and one sesquiterpene derivative, cordycepsetp A (4), together with six known compounds were isolated from Cordyceps militaris. The structures including absolute configurations of these new compounds, were unambiguously elucidated by spectroscopic data analysis and single crystal X-ray diffraction. Biological evaluation of compounds 1-4 showed that 3 displays anti-renal fibrotic activities in TGF-ß1 induced NRK-52e cells. Furthermore, DARTS coupled with LC-MS/MS analysis was used to identify candidate target proteins for 3. Subsequently, C1qbp knockdown using siRNA allowed us to validate the target protein of 3.

Mantidisflavin A: A Riboflavin Derivative Featuring a 6/6/6/5/5 Skeleton from the Egg Cases of the Insect Tenodera sinensis Saussure and Its Anti-Renal Fibrosis Activity.

Mantidisflavin A (1) was isolated from the egg cases of the Tenodera sinensis Saussure. It exhibits an unprecedented 6/6/6/5/5 skeleton, accompanied by the formation of two additional fused heterocycles through a novel C-C bond and an oxygen bridge on riboflavin backbone. The structure of 1 was identified by spectroscopic and computational methods. To assess the inhibitory effect against renal fibrosis, compound 1 was evaluated in TGF-ß1-induced rat kidney epithelial cells, and the results were compared to those of its precursor, riboflavin.

Dimeric diarylheptanoids with anti-inflammatory activity from Zingiber officinale.

Two previously undescribed chain diarylheptanoid derivatives (2-3), five previously undescribed dimeric diarylheptanoids (4-8), together with one known cyclic diarylheptanoid (1) were isolated from Zingiber officinale. Their structures were elucidated by extensive spectroscopic analyses (HR-ESI-MS, IR, UV, 1D and 2D NMR) and ECD calculations. Biological evaluation of compounds 1-8 revealed that compounds 2, 3 and 4 could inhibit nitrite oxide and IL-6 production in lipopolysaccharide induced RAW264.7 cells in a dose-dependent manner.

Identification of arnicolide C as a novel chemosensitizer to suppress mTOR/E2F1/FANCD2 axis in non-small cell lung cancer.

BACKGROUND AND PURPOSE: The mammalian target of rapamycin (mTOR) pathway plays critical roles in intrinsic chemoresistance by regulating Fanconi anaemia complementation group D2 (FANCD2) expression. However, the mechanisms by which mTOR regulates FANCD2 expression and related inhibitors are not clearly elucidated. Extracts of Centipeda minima (C. minima) showed promising chemosensitizing effects by inhibiting FANCD2 activity. Here, we have aimed to identify the bioactive chemosensitizer in C. minima extracts and elucidate its underlying mechanism. EXPERIMENTAL APPROACH: The chemosensitizing effects of arnicolide C (ArC), a bioactive compound in C. minima, on non-small cell lung cancer (NSCLC) were investigated using immunoblotting, immunofluorescence, flow cytometry, the comet assay, small interfering RNA (siRNA) transfection and animal models. The online SynergyFinder software was used to determine the synergistic effects of ArC and chemotherapeutic drugs on NSCLC cells. KEY RESULTS: ArC had synergistic cytotoxic effects with DNA cross-linking drugs such as cisplatin and mitomycin C in NSCLC cells. ArC treatment markedly decreased FANCD2 expression in NSCLC cells, thus attenuating cisplatin-induced FANCD2 nuclear foci formation, leading to DNA damage and apoptosis. ArC inhibited the mTOR pathway and attenuated mTOR-mediated expression of E2F1, a critical transcription factor of FANCD2. Co-administration of ArC and cisplatin exerted synergistic anticancer effects in the A549 xenograft mouse model by suppressing mTOR/FANCD2 signalling in tumour tissues. CONCLUSION AND IMPLICATIONS: ArC suppressed DNA cross-linking drug-induced DNA damage response by inhibiting the mTOR/E2F1/FANCD2 signalling axis, serving as a chemosensitizing agent. This provides insight into the anticancer mechanisms of ArC and offers a potential combinatorial anticancer therapeutic strategy.

N-containing phenolic compounds from Periplaneta americana with triple negative breast cancer inhibitory activity.

Eight previously undescribed compounds comprising pyrrole-2-carboxaldehyde derivatives, namely periplanpyrroles A-D (1-4), spirooxindole derivatives perispirooxindoles A (5) and B (6), and the phenolic compounds periplanetols G (7) and H (8), along with eight known compounds were isolated from the 70% ethanol extract of the whole bodies of Periplaneta americana. Their structures including absolute configurations were unambiguously identified by comprehensive spectroscopic analyses and computational methods. In addition, all compounds were evaluated for their activities against triple negative breast cancer in vitro. The wound healing assay revealed that 7, 9, and 11 significantly inhibit the migration of BT549 and MDA-MB-231 cells. Further observations made in Western blotting experiments showed that 7 could dose-dependently decrease the protein level of vimentin and N-cadherin in MDA-MB-231 and BT549 cells.

Dimeric N-Acetyldopamine Derivatives Featuring a Seco-Benzene System from the Insects Aspongopus chinensis and Periostracum cicadae.

Aspongamide F (1), a novel N-acetyldopamine (NADA) dimer possessing a 6/6/6 ring system, and (±)-aspongamides G (2) and H (3), rare NADA derivatives with fragmented benzene rings, were isolated from Aspongopus chinensis. (±)-Cicadamides C (4) and D (5), the first 1,4-Benzodioxane NADA dimers featuring a seco-benzene system, and (±)-cicadamides E (6) and F (7), the NADA dimers derivatives, were isolated from Periostracum cicadae. The structures of all compounds were elucidated by spectroscopic analyses and computational methods. A plausible biosynthetic pathway for compounds 1-5 was proposed. The biological assay revealed that (+)-4 and (-)-4 exhibit renal protection in a dose-dependent manner.

Novel spirooxindole alkaloid derivatives from the medicinal insect Blaps japanensis and their biological evaluation.

Blapspirooxindoles A-C (1-3), three novel spirooxindole alkaloids with a unique spiro[chromane-4,3'-indoline]-2,2'-dione motif, blapcumaranons A and B (4 and 5), two new 2-cumaranon derivatives, blapoxindoles A-J (6-15), ten new oxindole alkaloid derivatives, along with one known compound (16), were isolated from the whole bodies of Blaps japanensis. Their structures including absolute configurations were determined by using spectroscopic, X-ray crystallographic, and computational methods. Compounds 1-11 and 13 exist as racemic mixtures in nature, and their (-)- and (+)-antipodes were separated by chiral HPLC. Biological evaluations of these compounds were determined with multiple assays including anti-tumor, anti-inflammatory, and renal protection activities in vitro. Several compounds displayed effective activity in one or more assays.

Renoprotective Glycoside Derivatives from Zingiber officinale (Ginger) Peels.

As a widely consumed spice and traditional Chinese medicine, Zingiber officinale Roscoe (ginger) has been used in the treatment of nausea, coughs, and colds. In this article, 18 new glycosides (1-18) and six known analogues (19-24) were isolated from the peel of ginger. The planar structures of these compounds were determined by using HR-ESI-MS and extensive spectroscopic techniques (UV, IR, 1D-NMR, and 2D-NMR). Their relative and absolute configurations of the stereogenic centers in the new natural products were determined by analysis of NMR data, using a quantum mechanical NMR approach and time-dependent density functional theory based electronic circular dichroism calculations. The renal fibrosis activities of the isolated natural products together with those of 6-gingerol (6-Gi), 8-gingerol (8-Gi), and 10-gingerol (10-Gi) were evaluated in TGF-ß1 induced NRK-52E cells. Compounds 9, 10, 15, 22-24, 6-Gi, 8-Gi, and 10-Gi were found to be active toward extracellular matrix, indicating that they have potential renal fibrosis activities.

Correction: Non-peptide compounds from Kronopolites svenhedini (Verhoeff) and their antitumor and iNOS inhibitory activities.

[This corrects the article DOI: 10.3762/bjoc.19.59.].

Unusual acetylated flavonol glucuronides, oxyphyllvonides A-H with renoprotective activities from the fruits of Alpinae oxyphylla.

As a widely consumed spice and Traditional Chinese Medicine, Alpinae oxyphylla has been used to treat conditions such as diarrhea, ulcers, dementia, and enuresis. Fruits of A. oxyphylla were phytochemically studied and the bioactive constituents against renal fibrosis were identified. Eight previously undescribed acetylated flavonol glucuronides named oxyphyllvonides A-H (1-7 and 10), two known acetylated flavonol glucuronides (8 and 9), together with seven known flavone glycosides (11-17) were isolated from the fruits of A. oxyphylla. Among them, flavonol glucuronides were discovered in Zingiberaceae for the first time. The planar structures of 1-7 and 10 were determined using HRESIMS and extensive spectroscopic techniques (UV, IR, 1D-NMR, and 2D-NMR). The absolute configurations of the sugar moiety in these compounds were determined by using LC-MS analysis of acid-hydrolyzed derivatized monosaccharides. Biological evaluation showed that 7-10, 13, 14, 16 and 17 inhibit renal fibrosis in TGF-ß1-induced kidney proximal tubular cells. In addition, 7, 8 and 14 were superior to nootkatone in inhibiting Fibronectin expression. The finding has significant relevance to our ongoing research on the anti-renal fibrosis activity of A. oxyphylla.

Nine pairs of undescribed enantiomers from the resin of Styrax tonkinensis (Pierre) Craib ex Hart with anti-inflammatory activity.

Nine pairs of undescribed enantiomers, (±)-styraxoids A-I (1-9), were isolated from the resin of Styrax tonkinensis, and their structures were assigned by spectroscopic and computational methods. Compounds (±)-1 are a pair of degraded lignans, and the remaining compounds (±)-(2-9) are phenylpropanoid skeletons. Compounds (±)-8 and (±)-9 feature a 1,3-dioxolane moiety. The biological evaluation showed that both enantiomers of 1 could inhibit LPS-induced INOS and COX-2 in RAW264.7 cells in a dose-dependent manner.

Succipenoids A-C: A dimeric abietane and nor-abietane diterpenoids from fossil Chinese medicinal succinum and their anti-inflammatory potential.

An unprecedented dimeric abietane, succipenoid A (1), and two previously undescribed nor-abietane diterpenoids featuring a rarely occurring naphthalene ring or with a large conjugated system, succipenoids B and C (2 and 3), along with seven known diterpenoids (4-10) were isolated from the CH2Cl2 extract of succinum. The structures of these compounds, including their absolute configurations, were elucidated using spectroscopic and computational techniques. Notably, compounds 1-4 and 6-10 were isolated from succinum for the first time. In order to evaluate their anti-inflammatory potential, in vitro tests were conducted. The results demonstrated that compounds 1, 2, 4, and 6-10 exhibite dose-dependent inhibition of iNOS expression in lipopolysaccharide-induced RAW 264.7 cells.

Non-peptide compounds from Kronopolites svenhedini (Verhoeff) and their antitumor and iNOS inhibitory activities.

Six new compounds, including a tetralone 1, two xanthones 2 and 3, a flavan derivative 4, and two nor-diterpenoids 7 and 8, accompanied by two known flavan derivatives 5 and 6 and a known olefine acid (9) were isolated from whole bodies of Kronopolites svenhedini (Verhoeff). The structures of the new compounds were determined by 1D and 2D nuclear magnetic resonance (NMR) and other spectroscopic methods, as well as computational methods. Selected compounds were evaluated for their biological properties against a mouse pancreatic cancer cell line and inhibitory effects on iNOS and COX-2 in RAW264.7 cells.

Diverse alkaloids from the aerial parts of Aconitum carmichaelii and antiproliferative activity of costemline via inhibiting SIRT1/ROCK1/P-STAT3 pathways.

Six undescribed alkaloids together with 15 known alkaloids were isolated from the aerial parts of Aconitum carmichaelii. Their structures were elucidated extensively by NMR and HRESIMS spectroscopy. The absolute configurations of N-formyllaurotetanine, and the known compounds glaucine-ß-N-oxide and glaucine-α-N-oxide were established by electronic circular dichroism (ECD) spectra. Notably, it was the discovery of rare indole alkaloids from the genus Aconitum, and biosynthetic pathway of compounds 1 and 6 was deduced. Evaluation of the antiproliferative activity of these alkaloids demonstrated that costemline exhibited significant anti-proliferation effects against HCT116, SKOV3, and A549 cells with IC50 values of 5.6, 14.2, and 6.8 µM, respectively. Costemline could also inhibit the cell invasion activity of HCT116 cells. Mechanistic studies in HCT116 cells suggested that the antiproliferative activity of costemline was attributable to SIRT1/ROCK1/P-STAT3 pathways regulation. This study revealed the potential for developing and utilizing the aerial parts of Aconitum carmichaelii.

Racemic norneolignans from the resin of Ferula sinkiangensis and their COX-2 inhibitory activity.

Five new norneolignans sinkianlignans G-K (1-5), one phenolic compound ferulagenol A (6) and seven known compounds (7-13) were isolated from Ferula sinkiangensis. All the norneolignans were racemic mixtures, and chiral HPLC was used to further separate them. Their structures were assigned, including absolute configurations, using spectroscopic and computational methods. Biological evaluation showed that compounds 1-9 had significant COX-2 inhibitory activity with IC50 values ranging from 3.00 µM to 23.19 µM.

Lignans from the root of Valeriana jatamansi and their biological evaluation.

Investigation on the chemical components of Valeriana jatamansi Jones (Caprifoliaceae), a new lignan with pyran-ring, dipsalignan G (1), along with eight known compounds (2-9) were isolated. Their structures were elucidated by extensive analysis of 1D, 2D NMR and HR-ESI-MS spectroscopic data. Additionally, possible biosynthetic pathway of 1 was proposed. Finally, biological evaluation results showed that 8 had significant scavenging ability to ABTS and DPPH free radicals, with IC50 values of 1.35 ± 0.01 and 2.94 ± 0.01 µg/ml, respectively.