Passifetilactones A-E, Fatty Acid Lactones from the Fruit and Flowers of Passiflora foetida with Cytotoxic Activity.

Phytochemical investigation of the fruit and flowers of Passiflora foetida led to the isolation of 14 compounds, of which five are previously undescribed fatty acid lactones. Four 2-pyrones, passifetilactones A-D (1-4), and one furanone, passifetilactone E (5), were identified by analysis of spectroscopic and spectrometric data. The previously undescribed lactones were tested for cytotoxic activities against the cancer cell lines HeLa, A549, PC-3, KKU-055, and KKU-213A and two normal cell lines, Vero and MMNK-1. Passifetilactones B (2) and C (3) displayed good to mild cytotoxic activity, at IC50 3.7-25.9 µM and 12.2-19.8 µM, respectively, against six cell lines, but were weakly active against the MMNK-1 cell line. Passifetilactones B and C (2 and 3) showed cell apoptosis induction on the KKU-055 cell line in a flow cytometry experiment. Passifetilactone D (4) is an isolation artifact produced by purification over silica gel, but we demonstrated that it can also be slowly formed within the crude EtOAc extract. This is the first investigation of the flowers and the fruit of this plant.

Acrotrione B, a Prenylated and Highly Oxidized Xanthenoid with Antibacterial and Anti-proliferative Activities from the Roots of Acronychia pedunculata.

A new prenylated xanthenoid with a highly oxidized core, acrotrione B (1: ), together with six previously reported acetophenones (2:  - 7: ), were isolated from the roots of Acronychia pedunculata. The structures of the isolated compounds were elucidated by thorough analysis of their 1D and 2D NMR spectroscopic data. The relative and absolute configurations of acrotrione B were determined by electronic circular dichroism (ECD) calculations. Acrotrione B is an unusual, oxidized xanthenoid with a cyclohexadienone core that has not been previously reported. It thus represents a new skeletal type within the xanthenoid class. Acrotrione B (1: ) exhibited anti-proliferative activity against Hela (IC50 = 16.0 µM) and A549 (IC50 = 16.3 µM) cell lines. 5'-Prenylacrovestone (4: ) and acrovestone (5: ) were even more potent with IC50 values of 5.1 µM and 0.77 µM, respectively, against Hela cells and 11.8 µM and 1.13 µM, respectively, against A549 cells. Moreover, acrotrione B (1: ) displayed moderate antibacterial activities against Staphylococcus aureus, Bacillus cereus, and Bacillus subtilis, with MIC values in the range of 16 - 64 µg/mL. Finally, acropyrone (6: ) showed a significant suppression of lipopolysaccharide (LPS) induced NO production in murine macrophage J774.A1 cells (IC50 = 8.9 µM).

Scalarane Sesterterpenoids with Antibacterial and Anti-Proliferative Activities from the Mushroom Neonothopanus nambi.

Seven undescribed scalarane sesterterpenoids, nambiscalaranes B-H (1-7), together with two known compounds, nambiscalarane (8) and aurisin A (9) were isolated from the cultured mycelium of the luminescent mushroom Neonothopanus nambi. Their structures were elucidated by thorough analysis of their 1D and 2D NMR spectroscopic data. The absolute configurations of 1-8 were determined by electronic circular dichroism (ECD) calculations and optical rotation measurements. The isolated sesterterpenoids were evaluated against A549, HT29, HeLa, and HCT-116 cancer cell lines, and against five bacterial strains. Compounds 3, 5, and 7 showed strong cytotoxicity against HCT-116 cell line, with IC50 values ranging from 13.41 to 16.53 µM, and showed no cytotoxicity towards Vero cells. Moreover, compound 8 inhibited the growth of Bacillus subtilis with a MIC value of 8 µg/mL, which was equivalent to the MIC value of the standard kanamycin.

Secondary Metabolites and Their Biological Activity from Aspergillus aculeatus KKU-CT2.

The bioactive compounds of the fungus Aspergillus aculeatus strain KKU-CT2, have been studied. The crude extracts from this fungus showed good antimicrobial activity against human pathogens, including Gram-positive and Gram-negative bacteria and yeast-like fungi. Its chemical components were isolated and purified by chromatographic methods. The structures of the secondary metabolites were elucidated by spectroscopic methods (IR, 1H, and 13C NMR). They were identified as ergosterol peroxide (1), secalonic acid D (2), secalonic acid F (3), variecolin (4), variecolactone (5), and ergosterol (6). Compounds 1 and 4-6 are reported for the first time as fungal metabolites from this species. Compound 1 displayed inhibitory effects on HSV-1 with an IC50 of 11.01 µg/ml. Compounds 3, 4, and 6 exhibited antimalarial activity against Plasmodium falciparum with IC50 of 1.03, 1.47, and 5.31 µg/ml, respectively. Additionally, all compounds from A. aculeatus KKU-CT2 showed unprecedented anticancer activities against human epidermoid carcinoma in the mouth (KB) (compounds 1-6), human breast cancer (MCF-7) (compounds 2, 4, and 5), and human lung cancer cells (NCI-H187) (compounds 1-4 and 6). These results suggest that secondary metabolites from A. aculeatus KKU-CT2 might be interesting for further derivatization, targeting diseases such as cancer.

Chemical constituents from the roots of Zygostelma benthamii (Apocynaceae) and their anti-proliferative activities.

Phytochemical investigation of the roots of Zygostelma benthamii Baill. (Apocynaceae) led to the isolation of eleven known compounds. The isolated compounds were identified by analysis of physical and spectroscopic data. We report three phenolic compounds (1-3), four triterpenoids (4-7), one coumarin (8), one lignan (9), one pregnane terpenoid (10), and one diterpenoid (11). It is the first time that Zygostelma benthamii is investigated, and this is therefore the first study of the Zygostelma genus. In addition, compound 7 and 11 are reported from the Apocynaceae family for the first time. Compounds 6, 7, 10 and 11 were evaluated against several cancer cell lines (KKU-M213B, KKU-100, KKU-M055, and A549) and Vero cells. Compound 10 showed strong anti-proliferative activity against all the selected cell lines, with IC50 values in the range of 1.70-6.8 µg/mL.

Chemical constituents from Microstachys chamaelea (Euphorbiaceae) with cytotoxic and antioxidant properties.

Phytochemical investigation of Microstachys chamaelea led to the isolation and identification of fourteen known compounds after analysis of spectroscopic data. They consist of eight flavonoids (1-8), two benzoic acid derivatives (9-10), one brevifolin carboxylic acid derivative (11), one geraniinic acid derivative (12), shikimic acid (13), and ß-daucosterol (14). Remarkably, it is the second isolation of compound 12 from a natural source. Several isolates were evaluated against ten cancer cell lines and on a set of targets involved in oxidative stress, as no such assays were undertaken in previous works. Compound 7 showed moderate to strong cytotoxicity against eight cell lines (IC50 values of 6.0-39.0 µM), while compounds 2, 8, and 11 showed weak to moderate cytotoxicity. Compounds 1-3, 5, and 11-12 showed moderate to strong DPPH and XXO inhibitory activities (IC50 values of 13.1-16.5 and 6.0-69.0 µM, respectively).

Siamfuranones A-C, three novel furanone derivatives from the flowers of Uvaria siamensis and their biological activities.

Three previously undescribed furanone derivatives named siamfuranones A-C (1-3), together with 11 known compounds (4-14), were isolated from the flowers of Uvaria siamensis. Their planar structures were determined through analysis of spectrometric and spectroscopic evidence, while electronic circular dichroism (ECD) calculations were used to determine their absolute configurations. In addition, gauge-including atomic orbitals (GIAO) NMR chemical shift calculation, supported by the advanced statistical method DP4 plus, was used to confirm the relative configuration of siamfuranone B (2). All the isolated compounds were evaluated against two cancer cell lines (A549 and Hela), and screened for antibacterial activities. Furthermore, they were assessed for cytotoxicity against a normal cell line (Vero cell).

Anti-proliferative Effects of Pinocembrin Isolated From Anomianthus dulcis on Hepatocellular Carcinoma Cells.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer. Anomianthus dulcis (Dunal) J.Sinclair (syn. Uvaria dulcis) has been used in Thai traditional medicine in various therapeutic indications. Phytochemical constituents of A. dulcis have been isolated and identified. However, their effects on liver cancer and the associated mechanisms have not been elucidated. METHODS: Dry flowers of A. dulcis were extracted using organic solvents, and chromatographic methods were used to purify the secondary metabolites. The chemical structures of the pure compounds were elucidated by analysis of spectroscopic data. Cytotoxicity against HCC cells was examined using SRB assay, and the effects on cell proliferation were determined using flow cytometry. The mechanisms underlying HCC inhibition were examined by molecular docking and verified by Western blot analysis. RESULTS: Among 3 purified flavonoids, pinocembrin, pinostrobin, and chrysin, and 1 indole alkaloid (3-farnesylindole), only pinocembrin showed inhibitory effects on the proliferation of 2 HCC cell lines, HepG2 and Li-7, whereas chrysin showed specific toxicity to HepG2. Pinocembrin was then selected for further study. Flow cytometric analyses revealed that pinocembrin arrested the HCC cell cycle at the G1 phase with a minimal effect on cell death induction. Pinocembrin exerted the suppression of STAT3, as shown by the molecular docking on STAT3 with a better binding affinity than stattic, a known STAT3 inhibitor. Pinocembrin also suppressed STAT3 phosphorylation at both Tyr705 and Ser727. Cell cycle regulatory proteins under the modulation of STAT3, namely cyclin D1, cyclin E, CDK4, and CDK6, are substantially suppressed in their expression levels. CONCLUSION: Pinocembrin extracted from A. dulcis exerted a significant growth inhibition on HCC cells via suppressing STAT3 signaling pathways and its downstream-regulated genes.

Chemical constituents from the flowers of Anomianthus dulcis (Dunal) J. Sinclair.

Phytochemical investigation of the flowers of Anomianthus dulcis led to the isolation of eleven known compounds. The isolated compounds were identified by analysis of physical and spectroscopic (IR, 1 D and 2 D NMR) data. We report five flavonoids (1-4 and 10), two chalcone-sesquiterpenoids (5 and 6), one indole alkaloid (7), one triterpenoid (8), and a mixture of two phenolic compounds (9 and 11). Remarkably, it is the second isolation of sumadain A (5) and sumadain B (6) from a natural source. Compounds 5 and 6 were evaluated against several cancer cell lines, as the previous report lacked biological activity studies. Compound 6 showed strong cytotoxicity against Hela, HT-29, HCT-116, and A549 cell lines, with IC50 values in the range of 5.43-14.64 µg/mL.

A new polyphenolic isoprenylated acetophenone dimer from the stem bark of Acronychia pedunculata (L.) Miq.

A new acetophenone dimer, 5'-prenylacrovestone (1), together with nineteen known compounds (2-20), were isolated from the stem bark of Acronychia pedunculata (L.) Miq. Their structures were identified by thorough analysis of spectroscopic (IR, 1D and 2D NMR) and mass spectrometric data. The isolated compounds were tested against the bacterial pathogens MRSA, B. cereus, S. aureus and E. coli. Compound 3 demonstrated exceptionally potent antibacterial activity against each of the four strains (MIC values of 1 µg/mL).

Isopimarane-type diterpenoids from the rhizomes of Kaempferia galanga L. and their biological activities.

Fourteen isopimarane diterpenoids (1-14) were isolated from the rhizomes of Kaempferia galanga, including four new compounds (1-4). The isolated secondary metabolites were identified through analysis of spectroscopic (1 D and 2 D NMR) and mass spectrometric data, together with X-ray diffraction studies. Compounds 4-5, 7-11, and 13 showed strong antimalarial activities, with IC50 values in the range of 1.46-3.99 µg/mL. Moreover, compounds 4, 5, 8, and 12 showed cytotoxicity against KB cell line with IC50 values in the range of 6.13-38.2 µg/mL, while compounds 4, 5, and 12 showed cytotoxicity against MCF-7 cell line with IC50 values in the range of 11.75-47.4 µg/mL. Eventually, the isolated compounds were screened against six bacterial strains and Mycobacterium tuberculosis, demonstrating weak to moderate activities.

Acroflavone A, a new prenylated flavone from the fruit of Acronychia pedunculata (L.) Miq.

Phytochemical investigation of the fruit of Acronychia pedunculata (L.) Miq. led to the isolation of a new prenylated flavone, acroflavone A (1), together with eight known compounds (2-9). Their structures were elucidated by thorough analysis of mass spectrometric and NMR spectroscopic data. The isolated compounds were evaluated against several bacterial strains. Three known compounds (3-5) demonstrated antibacterial activities. Among them, acrovestone (5) proved equally or more potent than chloramphenicol against three out of the four strains tested.

Acroquinolones A and B, two polyphenolic isoprenylated acetophenone-quinolone hybrids with anti-proliferative activities from Acronychia pedunculata (L.) Miq.

Two new compounds belonging to a new class of acetophenone-alkaloid hybrids, acroquinolones A (1a) and B (1b), together with six known compounds, were isolated from the leaves of Acronychia pedunculata (L.) Miq. Their structures contain a quinolone and an acetophenone fragment, connected through an isopentyl unit. Attempts to isolate more hybrids from another sample collected at the same location but during a different season led to the isolation of a new tocopherol (2). The new compounds were evaluated against several cancer cell lines.

New iridoid glucosides from the roots of Rothmannia wittii (Craib) Bremek.

Phytochemical investigation of the roots of Rothmannia wittii led to the isolation of three new iridoid glucosides, named rothmanniosides A-C (1-3), and nine known compounds (4-12). Their structures, including their absolute configurations, were elucidated by thorough analysis of mass spectrometric and NMR spectroscopic data, together with CD calculations. Compounds 4 and 11 are reported from the Rubiaceae family for the first time.

Chemical constituents and their biological activities from the roots of diospyros filipendula.

Phytochemical investigation of Diospyros filipendula (Ebenaceae) resulted in the isolation of eighteen compounds. Their structures were identified by analysis of mass spectrometric and spectroscopic (IR, 1 D and 2 D NMR) data. We report three benzoic acid derivatives (1-3), one peptide (4), one coumarin (5), three phthalides (6-8), three steroids (9-11) and seven triterpenes (12-18). Nine compounds (1, 4-8, 10, 17 and 18) are reported from the Ebenaceae family for the first time while the other nine are new to the species D. filipendula. Compounds 7, 17 and 18 showed low to moderate cytotoxicity against NCI-H187 and Vero cell lines while compound 18 showed moderate cytotoxicity against KB cell line. In addition, compounds 17 and 18 showed moderate to significant antimalarial activity against Plasmodium falciparum.

New anthracene and anthraquinone metabolites from Prismatomeris filamentosa and their antibacterial activities.

An unusual, new anthracene natural product named filamentos A (1), two new anthraquinone derivatives named filamentos B (2) and C (3), together with sixteen known compounds (4-19), were isolated from the roots of the tree Prismatomeris filamentosa. Their structures were identified by analysis of mass and spectroscopic data (IR, 1D and 2D NMR). Twelve metabolites (1-6, 9, 12-14, 16-17) showed moderate antibacterial activities against a wide range of Gram-positive and Gram-negative bacteria such as B. subtilis, B. cereus, S. aureus, E. coli, P. aeruginosa and S. sonnei.

Assessment of antimycobacterial activities of pure compounds extracted from Thai medicinal plants against clarithromycin-resistant Mycobacterium abscessus.

BACKGROUND: Infection with Mycobacterium abscessus is usually chronic and is associated with clarithromycin resistance. Increasing drug resistance is a major public-health problem and has led to the search for new antimycobacterial agents. We evaluated the antimycobacterial activity, toxicity, and synergistic effects of several plant secondary metabolites against M. abscessus. METHODS: Twenty-three compounds were evaluated for antimycobacterial activity against thirty M. abscessus clinical isolates by broth microdilution to determine their minimum inhibitory concentration (MIC) values. Toxicity was evaluated using red and white blood cells (RBCs and WBCs). The compounds were used in combination with clarithromycin to investigate the possibility of synergistic activity. RESULTS: Five out of twenty-three compounds (RL008, RL009, RL011, RL012 and RL013) exhibited interesting antimycobacterial activity against M. abscessus, with MIC values ranging from <1 to >128 µg/mL. These extracts did not induce hemolytic effect on RBCs and displayed low toxicity against WBCs. The five least-toxic compounds were tested for synergism with clarithromycin against seven isolates with inducible clarithromycin resistance and seven with acquired clarithromycin resistance. The best synergistic results against these isolates were observed for RL008 and RL009 (8/14 isolates; 57%). CONCLUSIONS: This study demonstrated antimycobacterial and synergistic activities of pure compounds extracted from medicinal plants against clarithromycin-resistant M. abscessus. This synergistic action, together with clarithromycin, may be effective for treating infections and should be further studied for the development of novel antimicrobial agents.

A new secoiridoid glycoside and other constituents from the roots and flowers of Fagraea fragrans Roxb. (Gentianaceae).

A new secoiridoid glycoside, 3'-O-p-trans-coumaroylsweroside (1), together with twenty-nine compounds (2-30), were isolated from the roots and flowers of Fagraea fragrans Roxb. (Gentianaceae). Their structures were identified by analysis of mass spectrometric and NMR spectroscopic data. Compounds 2, 4, 6, 11 and 13-15 showed weak to moderate cytotoxicity against cholangiocarcinoma cancer cells lines (KKU-213, KKU-055 and KKU-214). We report the first phytochemical investigation of the roots and flowers of F. fragrans, as only the essential oil of the latter has been investigated.

Bioactive diterpenes from the aerial parts of Anisochilus harmandii.

Two new diterpenes, 4- EPI-triptobenzene L ( 1) and 12- O-deacetyl-6- O-acetyl-19- acetyloxycoleon Q ( 2), as well as eight known diterpenes ( 3- 10) were isolated from the aerial parts of Anisochilus hamandii. Structures of the isolated compounds were identified from spectroscopic evidence. Compounds 1, 2, 5, and 10 exhibited antiplasmodial activity against Plasmodium falciparum (IC (50) 4.70, 2.90, 3.03, and 7.20 microg/mL, respectively), while 3, 5, and 7 showed antimycobacterial activity against Mycobacterium tuberculosis (MIC 50 microg/mL). In addition, only 10 showed strong cytotoxicity against NCI-H187 cells (IC (50) 4.43 microg/mL).

A new tocotrienol from the roots and branches of Allophylus cobbe (L.) Raeusch (Sapindaceae).

A new tocotrienol, 5-hydroxy-8-methyltocotrienol (1) was isolated from the roots and branches of A. cobbe (L.) Raeusch, together with seventeen known compounds (2-18). Their structures were elucidated by analysis of spectroscopic data and by comparison of 1H and 13C NMR data with previous literature reports. This is the first phytochemical investigation of the roots and branches of Allophylus cobbe (L.) Raeusch.