α-Glucosidase Inhibitory Activity of Prenylated Pyranocoumarins from Clausena excavata: Mechanism of Action, ADMET and Molecular Docking.

Three naturally occurring prenylated pyranocoumarins, nordentatin (1), dentatin (2), and clausarin (3), isolated from the roots of Clausena excavata (Family Rutaceae), and O-methylclausarin (4) which was obtained by methylation of 3, were investigated for their α-glucosidase inhibitory activity. The mechanism of action and the in silico prediction of their physicochemical and ADMET properties as well as the molecular docking were also studied. Compounds 1-4 exhibited stronger α-glucosidase inhibitory activity than the positive control, acarbose, through a non-competitive mechanism. Among them, 3 exhibited the highest activity, with an IC50 of 8.36 µM, which is significantly stronger than that of acarbose (IC50=430.35 µM). The prenyl group on C-3 and the hydroxyl group on C-5 in 3 may play important roles in enhancing the activity. Calculated physicochemical and ADMET parameters of 1-4 satisfied the Lipinski's and Veber's rules. Molecular simulation analysis indicated they are promising drug candidates with no hepatotoxicity. Compound 3 exhibited potent activity in the experiment and demonstrated good drug properties based on the calculations. A molecular docking study revealed that 3 showed H-bonding and π-π stacking interactions with selective Phe321, as well as interactions with thirteen other amino acid residues of the α-glucosidase.

A New Isoflavone Xylopyranoside and Isoflavone Derivatives from the Roots of Ochna integerrima and Their DPPH Radical Scavenging Activity.

O chna integerrima (Louri) Merr. is one of the two species of the genus Ochna (family Ochnaceae) found in Thailand. Its bark is used in traditional Thai medicine to treat digestive disorders. Phytochemical investigation of the crude MeOH extract of the root woods of O. integerrima furnished an unreported isoflavone glycoside, gerontoisoflavone A-4'-O-ß-D-xylopyranoside (1), together with the previously described irisolone methyl ether (2), iriskumaonin methyl ether (3), iriskumaonin (4), gerontoisoflavone A (5), isoprunetin (6), a flavone glycoside, vitexin (7), and a chromone derivative, lophilone A (8). The structure of 1 was elucidated by 1D and 2D NMR spectral analysis as well as HRMS data. Compounds 1-7 were evaluated for their 2,2-diphenyl-1-picrylhydrazil radical (DPPH●) scavenging activity and antiplasmodial activity against a chloroquine- and pyrimethamine-resistant strain of Plasmodium falciparum (K1). Compounds 5 exhibited strongest scavenging activity, with a scavenging concentration at 50% (SC50) of 137.7 mM, while 4 and 6 displayed weak scavenging activity, with SC50 values of 4 and 5 times higher than that of 5. None of the tested compounds showed antiplasmodial activity against P. falciparum (K1) at a concentration of 5 mg/mL.

Bioassay-Guided Isolation and Identification of Antiplasmodial Compounds from the Stem Bark of Clausena excavata.

Clausena excavata is a medicinal plant widely distributed in Southeast Asia. It is used for a variety of indications, including to treat malaria. In our present study, a phytochemical study of the methanol extract from the stem bark of C. excavata led to the isolation of five pyranocoumarins, nordentatin (1: ), dentatin (2: ), kinocoumarin (3: ), clausarin (4: ), and clausenidin (5: ), and a coumarin, 8-hydroxy-3″,4″-dihydrocapnolactone-2',3'-diol (6: ). The isolation of compound 6: from C. excavata and the antiplasmodial activities against a multidrug-resistant K1 strain of Plasmodium falciparum of 1, 3: , and 5: were reported for the first time. Compounds 3: and 4: exhibited potent antiplasmodial activities with EC50 values of 1.10 and 0.58 µM, respectively, while 1: and 5: had EC50 values of 5.62 and 7.15 µM, respectively. A prenyl group attached to the C-3 or C-12 position on the pyranocoumarin ring probably plays an important role on the activity. A hydroxyl group at the C-10 position is also likely to enhance the activity.

Bioactive compounds from the roots of Strophioblachia fimbricalyx.

Eight new compounds, fimbricalyxs B-D (1-3), fimbricalyxanhydrides A and B (4, 5), and fimbricalyxlactones A-C (6-8), together with three known compounds, trigonostemone (9), 3,6,9-trimethoxyphenanthropolone (10), and fimbricalyx A (11), were isolated from the roots of Strophioblachia fimbricalyx. The structures of the new compounds were elucidated on the basis of their spectroscopic data and, in the case of compounds 2, 4, and 7, confirmed by single-crystal X-ray crystallographic analysis. Compounds 1-4 and 8 were evaluated for their cytotoxicity (KB, MCF7, and NCI-H187 cancer cells) and antiplasmodial activity (Plasmodium falciparum, K1 multidrug-resistant strain). Fimbricalyx B (1) exhibited potent antiplasmodial activity with an IC50 value of 0.019 µM, while 4 was cytotoxic toward NCI-H187 cancer cells and showed antiplasmodial activities with IC50 values of 5.7 and 3.9 µM, respectively. In addition, the X-ray structure of 10 and the antiplasmodial activity of 11 are reported herein for the first time.

Fractionation of an Extract of Pluchea odorata Separates a Property Indicative for the Induction of Cell Plasticity from One That Inhibits a Neoplastic Phenotype.

Introduction. Several studies demonstrated that anti-inflammatory remedies exhibit excellent anti-neoplastic properties. An extract of Pluchea odorata (Asteraceae), which is used for wound healing and against inflammatory conditions, was fractionated and properties correlating to anti-neoplastic and wound healing effects were separated. Methods. Up to six fractionation steps using silica gel, Sephadex columns, and distinct solvent systems were used, and eluted fractions were analysed by thin layer chromatography, apoptosis, and proliferation assays. The expression of oncogenes and proteins regulating cell migration was investigated by immunoblotting after treating HL60 cells with the most active fractions. Results. Sequential fractionations enriched anti-neoplastic activities which suppressed oncogene expression of JunB, c-Jun, c-Myc, and Stat3. Furthermore, a fraction (F4.6.3) inducing or keeping up expression of the mobility markers MYPT, ROCK1, and paxillin could be separated from another fraction (F4.3.7), which inhibited these markers. Conclusions. Wound healing builds up scar or specific tissue, and hence, compounds enhancing cell migration support this process. In contrast, successful anti-neoplastic therapy combats tumour progression, and thus, suppression of cell migration is mandatory.

Characterisation of indole alkaloids and phenolic acids from wild mushroom Tropicoporus linteus and its chemical profiles compared with other Sanghuang mushrooms.

Two new indole alkaloids, 1-methylindole-7-methoxy-3-carboxaldehyde (2) and 7-methoxyindole-3-carboxaldehyde (4), together with 7-methoxyindole-3-carboxylic acid methyl ester (1) and 1-methylindole-3-carbaldehyde (3) were isolated from the fruiting bodies of wild Sanghuang mushroom Tropicoporus linteus (TL663). TLC, 1H-NMR and LC-MS chemical profiles of this mushroom compared with other three genera of wild Sanghuang mushroom extracts were investigated. The TLC, 1H-NMR and LC-MS profiles of TL663 and Sanghuangporus sanghuang (SS664) were similar and significantly different from other mushrooms. These two samples indicated the same TLC chromatograms by showing prominent bands of 1 - 4 when observed under UV 254 nm and having sharp aldehyde proton signals of 3-carboxaldehyde indole type in 1H-NMR spectra. From LC-MS analyses, peaks of isolated compounds 1 - 4 and indole-3-carboxaldehyde (5) in TL663 extract and peaks of protocatechuic acid (6), caffeic aldehyde (7), caffeic acid (8) and 3,4-dihydroxybenzalacetone (9) phenolic acids in TL663 fraction were identified.

Ferruginenes A-C from Rhododendron ferrugineum and their cytotoxic evaluation.

Three new compounds, ferruginenes A (1) and B (2) and a mixture of C-5'(R) and C-5'(S) ferruginene C (3) diastereomers, have been isolated from a cytotoxic chloroform-soluble fraction of the leaves of Rhododendron ferrugineum together with 12 known compounds. The structures of these new compounds were elucidated by analyses of NMR spectroscopic and mass spectrometric data. Compounds 1-3 were tested for their cytotoxicity against three human cancer cell lines, namely, HL-60, HeLa-S3, and MCF-7.

Cytotoxic and antiplasmodial compounds from the roots of Strophioblachia fimbricalyx.

The known phenanthrenone trigonostemone (1), along with a new phenanthrenone, 9-O-demethyltrigonostemone (2), and two new phenanthropolones, 3,6,9-trimethoxyphenanthropolone (3) and 4,6,9-trimethoxyphenanthropolone (4), were isolated from the roots of Strophioblachia fimbricalyx. Compound 2 showed cytotoxicity against NCI-H187, KB, and MCF7 cancer cells with IC50 values of 0.8, 0.8, and 2.9 microg/mL, respectively, while 3 and 4 showed reduced cytotoxicity. Compounds 2 and 3 displayed antiplasmodial activity in vitro (IC50 values of 2.7 and 3.2 microg/mL, respectively) against Plasmodium falciparum (K1, resistant strain). In addition, the antioxidant activity of 1-4 toward DPPH radicals was determined, but only compound 2 showed any discernible activity.

Colony Characteristics, Nucleoside Analog Profiles, and Genetic Variations of Medicinal Fungus Polycephalomyces nipponicus (Ascomycetes) Isolates from Northeast Thailand.

The entomopathogenic fungus Polycephalomyces nipponicus is known to have activity against human pathogenic bacteria and the malaria pathogen; however, information about its genetic variation is limited. In this study, cicada nymphs infected with entomopathogenic fungi were collected from various locations in the northeast of Thailand. Internal transcribed spacer sequencing was used to identify the fungal pathogen P. nipponicus. A total of 36 isolates of P. nipponicus from 6 provinces were investigated for variations in fungal morphology, nucleoside analog content, and genetics. The results showed that colony morphology varied depending on the strain of the tested fungi, without influence from its geographic origin. A similar finding was observed with regard to the production of nucleoside analog content. Interestingly, the important bioactive compound adenosine was detected in the mycelial extract of all 36 isolates. This indicates that P. nipponicus could possibly be used as a source of potential therapeutic bioactive compounds. In addition, random amplified polymorphic DNA analysis, as supported by the Nei Index and Shannon Index values, showed high genetic variation within and between the populations. These findings represent what is, to our knowledge, the first information on the colony morphology, adenosine analog profile, and genetic variation of P. nipponicus.

Transformation of an irregularly bridged epidithiodiketopiperazine to trichodermamide A.

[reaction: see text] An unusually bridged epidithiodiketopiperazine, pretrichodermamide A (3), was isolated from the fungus Trichoderma sp. BCC 5926. During the extensive effort to crystallize 3 for X-ray crystallographic analysis, conversion of this compound to trichodermamide A with coproduction of S(8) occurred.

Effects of Ethyl Acetate Extracts from the Polycephalomyces nipponicus Isolate Cod-MK1201 (Ascomycetes) against Human Pathogenic Bacteria and a Breast Cancer Cell Line.

This study aimed to identify a suitable organic solvent for extracting bioactive compounds from Polycephalomyces nipponicus and to evaluate the antibacterial and anticancer activities of the extracts obtained. Only extracts obtained with ethyl acetate exhibited antibacterial activity, so ethyl acetate was chosen for large-scale extraction. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against Gram-positive and Gram-negative human pathogenic bacteria of the 3 ethyl acetate-derived extracts-ethyl acetate extract from P. nipponicus (PN-ME), ethyl acetate extract after defatting (PN-ME*), and ethyl acetate extract after refluxation (PN-ME')-were determined. PN-ME' exhibited the most potent activity, inhibiting 12 of the 18 test bacteria, especially Bacillus cereus ATCC 11778 and Vibrio cholera (O1) DMST 9700, with low MIC and MBC values. PN-ME* showed greater inhibitory activity than PN-ME. The effects of the extracts on bacterial cell morphology were also determined. After 120 minutes of treatment with PN-ME* or PN-ME', B. cereus ATCC 11778 exhibited an abnormal rod-shaped cell structure, with some cells elongated to multiple times their original size and others appearing collapsed. V cholera (O1) DMST 9700 cells showed shrinkage and the formed subsurface cavities. PN-ME* and PN-ME' also inhibited the growth of MCF-7 breast cancer cells. In conclusion, the fungal isolate P. nipponicus Cod-MK1201 represents a source of antibacterial and anti-breast cancer compounds.

A novel ascochlorin glycoside from the insect pathogenic fungus Verticillium hemipterigenum BCC 2370.

Vertihemipterin A, the ascochlorin glycoside, and its aglycone, 4',5'-dihydro-4'-hydroxyascochlorin, were isolated from the insect pathogenic fungus Verticillium hemipterigenum BCC 2370. A new analog, 8'-hydroxyascochlorin, and five known compounds, ascochlorin, LL-Z1272delta, 8',9'-dehydroascochlorin, ascofuranone and ascofuranol, were also isolated from the same fermentation broth. Structures of these compounds were elucidated by spectroscopic methods. Stereochemistry of the known compound, 4',5'-dihydro-4'-hydroxyascochlorin, was addressed by NMR spectral analyses and the modified Mosher's method. Antiviral (HSV-1) and cytotoxic activities of these ascochlorin analogs were evaluated.

Evaluation of antimycobacterial, antiplasmodial and cytotoxic activities of preussomerins isolated from the lichenicolous fungus Microsphaeropsis sp. BCC 3050.

A new preussomerin isomer, 3'-O-demethylpreussomerin I, five known preussomerins E - I, and two known deoxypreussomerins, deoxypreussomerin A and bipendensin (palmarumycin C11), were isolated from a lichenicolous fungus Microsphaeropsis sp. BCC 3050. These structures were elucidated by spectroscopic methods, especially 1D- and 2D-NMR. The preussomerins were evaluated for their antimycobacterial and antiplasmodial activities as well as cytotoxicity against KB, BC-1 and vero cell lines.