Bo Hou

Two New Classes of T-Type Calcium Channel Inhibitors with New Chemical Scaffolds from Ganoderma cochlear.

T-type calcium channel (TTCC) inhibitors hold great potential for the treatment of a variety of neurological disorders. Cochlearoids A-E (1-5), five pairs of dimeric meroterpenoid enantiomers, and cochlearines A (6) and B (7), two pairs of enantiomeric hybrid metabolites, were isolated and characterized from Ganoderma cochlear. Biological evaluation found that compounds (+)-1, (-)-3, and (±)-6 significantly inhibited Cav3.1 TTCC and showed noticeable selectivity against Cav1.2, Cav2.1, Cav2.2, and Kv11.1 (hERG) channels.

Melokhanines A–J, Bioactive Monoterpenoid Indole Alkaloids with Diverse Skeletons from Melodinus khasianus

The new melokhanines A-J (1-10) and 22 known (11-32) alkaloids were isolated from the twigs and leaves of Melodinus khasianus. The new compounds and their absolute configurations were elucidated by extensive analysis of spectroscopic, X-ray diffraction, and computational data. Melokhanine A (1), composed of a hydroxyindolinone linked to an octahydrofuro[2,3-b]pyridine moiety, is an unprecedented monoterpenoid indole alkaloid. Melokhanines B-H (2-8) possess a new 6/5/5/6/6 pentacyclic indole alkaloid skeleton. Alkaloids 1-16, 25-27, 31, and 32 showed the best antibacterial activity against Pseudomonas aeruginosa (MIC range 2-22 μM). Among the seven dermatophytes tested, compound 1 showed significant inhibitory activity against Microsporum canis, M. ferrugineum, and Trichophyton ajelloi (MIC range 38-150 μM), i.e., half the efficacy of the positive control, griseofulvin.

(+/-)-Aspongamide A, an N-Acetyldopamine Trimer Isolated from the Insect Aspongopus chinensis, Is an Inhibitor of p-Smad3

(±)-Aspongamide A (1), an unusual trimer of N-acetyldopamine (NADA) bearing a novel tetrahydrobenzo[a]dibenzo[b,e][1,4]dioxine structure, and a pair of NADA dimeric enantiomers (2) were isolated from Aspongopus chinensis. The structures of compounds 1 and 2 were assigned using spectroscopic methods. Compound 1 was found to be an inhibitor of Smad3 phosphorylation in transforming growth factor-β1 (TGF-β1) induced rat renal proximal tubular cells and suppressed extracellular matrix expression in mesangial cells under diabetic conditions.

Cytotoxic bibenzyl dimers from the stems of Dendrobium fimbriatum Hook

The bioassay-guided chemical investigation of the stems of Dendrobium fimbriatum Hook led to the isolation of seven first reported bibenzyl dimers with a linkage of a methylene moiety, fimbriadimerbibenzyls A-G (1-7), together with a new dihydrophenanthrene derivative (S)-2,4,5,9-tetrahydroxy-9,10-dihydrophenanthrene (8) and thirteen known compounds (9-21). The structure of the new compound was established by spectroscopic analysis. Biological evaluation of bibenzyl derivatives against five human cell lines indicated that seven of those compounds exhibited broad-spectrum and cytotoxic activities with IC50 values ranging from 2.2 to 21.2 μM. Those rare bibenzyl dimers exhibited cytotoxic activities in vitro and the cytotoxicity decreased as the number of oxygen-containing groups in the structure decreases.

(+/-)-Uncarilins A and B, Dimeric Isoechinulin-Type Alkaloids from Uncaria rhynchophylla

(±)-Uncarilins A and B (1a/1b and 2a/2b), two pairs of unusual dimeric isoechinulin-type enantiomers with a symmetric four-membered core, were isolated from Uncaria rhynchophylla driven by LCMS-IT-TOF analyses. Their structures were elucidated by extensive 1D and 2D NMR spectra, X-ray diffraction, and ECD spectroscopic data. (-)-Uncarilin B (2a) showed activities on MT1 and MT2 receptors with agonistic rates of 11.26% and 52.44% at a concentration of 0.25 mM.

Seco-Dendrobine-Type Alkaloids and Bioactive Phenolics from Dendrobium findlayanum

Investigation of the 95% EtOH extract of stems of Dendrobium findlayanum afforded four new seco-dendrobines, findlayines A-D (1-4); two known dendrobines, dendrobine (5) and 2-hydroxydendrobine (6); and four new phenolic compounds, dendrofindlaphenols A-C (7, 9, and 10) and 6″-de-O-methyldendrofindlaphenol A (8). Compounds 1 and 2 are the first seco-dendrobines possessing a seven-membered lactam moiety, with 3 and 4 derived from the oxidative cleavage of the C-2-C-3 bond of dendrobine. The structures were established using spectroscopic methods and by comparison with literature data. The absolute configurations of 1-4 were confirmed via single-crystal X-ray diffraction data. Cytotoxic activity assays against HL-60, SMMC-7721, A-549, MCF-7, and SW480 human cancer cell lines revealed IC50 values ranging from 2.3 to 5.3 μM for compound 7, from 19.4 to 34.4 μM for 8, and from 49.4 to 96.8 μg/mL for the EtOAc extract. An assay of the inhibition of NO production with RAW 264.7 cells indicated that 8 had an IC50 value of 21.4 μM, and the EtOAc extract, 10.5 μg/mL. The EtOAc extract possessed DPPH radical scavenging activity of 69.93% at 100 μg/mL.

Clinoposides A–F: meroterpenoids with protective effects on H9c2 cardiomyocyte from Clinopodium chinense

Six novel flavonoid–triterpene saponin meroterpenoids, clinoposides A–F (1–6), with two unusual skeletons were isolated from Clinopodium chinense. Clinoposides A–F represent a new class of isopentenyl flavonoid saponin. Their structures were determined based on spectroscopic data and chemical methods. The relative and absolute stereochemistries were assigned using a combination of NOESY and ECD. A possible biogenetic pathway for 1–6 is proposed. The protective effects of clinoposides A–F against H2O2-induced H9c2 cardiomyocyte injury were tested, and all compounds exhibited significantly dose-dependent effects, clinoposides B, D and F showed better protective effects as evidence by increased levels of SOD, CAT and GSH-Px but reduced MDA, LDH, caspase-3 and -9 levels.

Stilbenes with anti-inflammatory and cytotoxic activity from the rhizomes of Bletilla ochracea Schltr

Four new dihydrophenanthrenofuran, bleochranols A-D (1-4), along with 21 known compounds including phenanthrenes (5-14) and bibenzyls (15-25) were isolated and elucidated from the rhizomes of Bletilla ochracea. Combination of 1D/2D NMR techniques and the Electronic Circular Dichroism (ECD) spectroscopy based on the empirical helicity rules, chemical structure of those isolates were determined. All the compounds were evaluated for cytotoxicity against HL-60, SMMC-7721, A-549, MCF-7 and SW480 human cancer cell lines by MTS assay and anti-inflammatory activity by nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages. Among the 25 tested compounds, bleochranol A (1) showed remarkable cytotoxic activity against HL-60, A-549, and MCF-7 with IC50 values of 0.24 ± 0.03, 3.51 ± 0.09 and 3.30 ± 0.99 μM respectively. The anti-inflammatory assay showed that compound 12 exhibited most potential activity against NO production in RAW 264.7 macrophages with IC50 2.86 ± 0.17 μM. The results indicated that the main chemical constituents of B. ochracea were phenanthrene and bibenzyl and similar to that of B. striata.

Iridoids and bis-iridoids from Patrinia scabiosaefolia

Ten new iridoids, patriscabioins A–J (1–10), and three unique bis-iridoids, patriscabiobisins A–C (11–13), together with seven known analogues, have been identified from whole plants of Patrinia scabiosaefolia. Compounds 1 to 8 are a series of 5,6-dihydrovaltrate hydrins with unique substituent groups in the Valerianaceae family such as isovaleryl and 3-methylcrotonyl. Furthermore, compounds 11 and 12 are the first reported bis-iridoids with two units connected by a 1,3-dioxane group, whereas compound 13 is linked by an ether bond between two units. The structures of all the compounds were established on the basis of extensive spectroscopic analysis as well as experimental and calculated ECD spectra. Compounds 1 and 3 showed moderate inhibitory activities on AChE with IC50 values of 37.6 and 10.5 µM, respectively. Moreover, compounds 1, 3, and 5 also showed moderate cytotoxic activity against HL-60, with IC50 values ranging from 1.2 to 27.6 µM.

Synthesis, antioxidant activity, and density functional theory study of catechin derivatives

Catechin derivatives were synthesized, and their structures were characterized by 1H-NMR, 13C-NMR, and mass spectrometry. The target compounds were evaluated for their antioxidant activities. Compound 2 showed the highest antioxidant activity, with an IC50 value of 136.637 μM, whereas methylated derivatives showed weak activity. Density functional theory (DFT) studies were carried out at the B3LYP/6-311++G (d, p) level of theory. According to the geometries, molecular electrostatic potential (MEP), bond dissociation enthalpy (EDE), the HOMO and LUMO, and reactivity indices (η, μ, ω, ω+, and ω−), we predicted the free radical scavenging capacity of catechins and their derivatives from their structures. We also found that the B-ring of catechins is a stronger electron donor than the A- or D-ring, and that there is a good relationship between the bond dissociation enthalpies (BDEs). These theoretical results will be helpful in the development of new or modified antioxidant compounds.