Antimalarial and cytotoxic activities of pregnene-type steroidal alkaloids from Holarrhena pubescens roots.

The phytochemical investigation of an alkaloidal extract of Holarrhena pubescens roots led to the isolation and identification of a new pregnene-type alkaloid, mokluangin D (1), together with nine known steroidal alkaloids (2-10). The structure of the new metabolite was determined on the basis of spectroscopic analyses including 1D- and 2D-NMR spectroscopy and mass spectrometry. Compounds 3 and 4 showed potent antimalarial activity against Plasmodium falciparum K1 stain with IC50 values of 1.2 and 2.0 µM, respectively, and showed weak cytotoxic activity against the NCI-H187 cell line with IC50 values of 27.7 and 30.6 µM, respectively. The substituent groups at C-3 and the carbonyl group at C-18 are important for the activity against the P. falciparum K1 stain.

2-Phenylnaphthalenes and a polyoxygenated cyclohexene from the stem and root extracts of Uvaria cherrevensis (Annonaceae).

Three new 2-phenylnaphthalene derivatives, cherrevenaphthalenes A-C (1-3), and a new polyoxygenated cyclohexene derivative, (-)-uvaribonol F (4) together with six known compounds, 5-10, were isolated from the stem and root extracts of Uvaria cherrevensis (Annonaceae). The structures of all isolated compounds were elucidated by spectroscopic analysis. The structures of 3 and 4 were further confirmed by single crystal X-ray diffraction methods. Compound 2 exhibited modest antiplasmodial activity against the P. falciparum stains TM4/8.2 and K1CB1 with IC50 values of 18.8±3.63 and 23.4±4.08µM, respectively, and weak cytotoxicity to a Vero cell line. Furthermore, compound 4 displayed cytotoxic activity against a KB cell line with an IC50 value of 22.1±0.42µM but was non-cytotoxic to the Vero cell line. Compound 5 revealed stronger cytotoxicity towards the KB cell line, with an IC50 value of 5.05±0.86µM and was nearly equally cytotoxic to the Vero cell line.

New Benzophenones and Xanthones from Cratoxylum sumatranum ssp. neriifolium and Their Antibacterial and Antioxidant Activities.

Two new benzophenones (1 and 2) and four new xanthones (4-6 and 17) together with 24 known compounds (3, 7-16, and 18-30) were isolated from the roots and twigs of Cratoxylum sumatranum ssp. neriifolium. Their structures were elucidated by spectroscopic methods. Compounds 5 and 26 showed antibacterial activity against Micrococcus luteus, Bacillus cereus, and Staphylococcus epidermis with minimum inhibitory concentrations ranging from 4 to 8 µg/mL, whereas compounds 7, 20, and 26 displayed selective antibacterial activities against Staphylococcus aureus (8 µg/mL), Salmonella typhimurium (4 µg/mL), and Pseudomonas aeruginosa (4 µg/mL), respectively. The radical scavenging effects of some isolated compounds were investigated. Compounds 11 and 21 exhibited potent activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) with IC50 values of 7.0 ± 1.0 and 6.0 ± 0.2 µM, respectively.

A New Cytotoxic Clerodane Diterpene from Casearia graveolens Twigs.

The first phytochemical investigation of Casearia graveolens twigs led to the isolation and identification of a new clerodane diterpene, caseariagraveolin (1), together with six known compounds (2-7). Their structures were elucidated by intensive analysis of their spectroscopic data. Compound 1 showed strong cytotoxicity against oral cavity and breast cancer cell lines with IC50 values of 2.48 and 6.63 µM, respectively.

Xanthones from Garcinia propinqua Roots.

Phytochemical investigation of Garcinia propinqua roots led to the isolation and identification of a new xanthone, doitunggarcinone D (1), together with 15 known compounds (2-16). Their structures were elucidated by intensive analysis of spectroscopic data. Compounds 3, 6, 7, 14, 15 and 16 exhibited strong antibacterial activity against Bacillus subtilis TISTR 088 with MIC values in the range of 1-4 µg/mL. Compounds 3, 7, 10 and 14 also showed good antibacterial activity against B. cereus TISTR 688 with MIC values ranging from 4-8 µg/mL.

Antimalarial Oxoprotoberberine Alkaloids from the Leaves of Miliusa cuneata.

Five new oxoprotoberberine alkaloids, miliusacunines A-E (1-5), along with nine known compounds, 6-14, were isolated from an acetone extract of the leaves and twigs of Miliusa cuneata. Their structures were elucidated by spectroscopic analysis. All isolated compounds were evaluated for their cytotoxicities against the KB and Vero cell lines and for antimalarial activities against the Plasmodium falciparum strains TM4 and K1 (a sensitive and a multi-drug-resistant strain, respectively). Compound 1 showed in vitro antimalarial activity against the TM4 strain, with an IC50 value of 19.3 ± 3.4 µM, and compound 2 demonstrated significant activity against the K1 strain, with an IC50 value of 10.8 ± 4.1 µM. Both compounds showed no discernible cytotoxicity to the Vero cell line at the concentration levels evaluated.

Acetylcholinesterase inhibitory activity and molecular docking study of steroidal alkaloids from Holarrhena pubescens barks.

An alkaloidal extract of the bark of Holarrhena pubescens showed several inhibition zones of acetylcholinesterase (AChE) inhibitor, using a bioautographic assay. Activity-guided fractionation afforded three new steroidal alkaloids, mokluangins A-C (1-3), together with three known compounds, antidysentericine (4), holaphyllamine (5), methylholaphyllamine (6). All structures were elucidated by analysis of NMR and MS spectroscopic data. Compound 2 showed moderate antibacterial activity against Bacillus subtilis and Escherichia coli with the MIC value of 16 µg/mL, while compound 3 exhibited moderate selective activity against E. coli with the MIC value of 16 µg/mL. In addition, compounds 1-4 also showed strong AChE inhibiting activity with IC50 values ranging from 1.44 to 23.22 µM. Molecular docking calculations were also performed and the results demonstrated that all compounds can bind at the aromatic gorge of AChE with estimated binding free energies correlated well with the in vitro inhibitory profiles. Hydrophobic and hydrogen bonding interactions contribute mainly to the binding of the alkaloids where the substituents at C-3 serving as key functional groups for the AChE inhibition. Our results will allow the development of new AChE-inhibitors based on steroidal alkaloid skeleton bearing the cyclic amide moiety.

Cytotoxic and Antimalarial Alkaloids from the Twigs of Dasymaschalon obtusipetalum.

One new p-quinonoid aporphine alkaloid, obtusipetadione (1), and eleven known compounds (2-12) were isolated from the acetone extract of the twigs of Dasymaschalon obtusipetalum. Their structures were elucidated by spectroscopic methods. The cytotoxic and antimalarial activities of the isolated compounds were evaluated. Compound 1 showed significant in vitro antiplasmodial activity against the P. falciparum strains TM4 and K1 (multidrug resistant strain) with IC50 values of 2.46 ± 0.12 and 1.38 ± 0.99 µg/mL, respectively with no cytotoxicity. Compound 9 had more modest antiplasmodial activity, but significant cytotoxicity.

Bioactive prenylated xanthones from the young fruits and flowers of Garcinia cowa.

Five new xanthones, garciniacowones A-E (1-5), together with 14 known xanthones, 6-19, were isolated from the young fruits and fresh flowers of Garcinia cowa. The structures of 1-5 were elucidated by analysis of their 1D and 2D NMR spectra and mass spectrometric data. The compounds 1-19 were tested in vitro for their antimicrobial activity and for their ability to inhibit α-glucosidase. Compounds 16 and 17 showed the most potent α-glucosidase inhibitory activity, with IC50 values of 7.8 ± 0.5 and 8.7 ± 0.3 µM, respectively. Compounds 8, 9, and 19 showed antibacterial activity against Bacillus subtilis TISTR 088 with identical MIC values of 2 µg/mL, while 8, 10, and 19 exhibited antibacterial activity against Bacillus cereus TISTR 688 with identical MIC values of 4 µg/mL.

Dammarane terpenoids from the fruits of Dysoxylum mollissimum.

Two new dammaranes, dysomollisol (1) and dysomollisone (2), along with seven known compounds (3-9) were isolated and identified from the fruits of Dysoxylum mollissimum. The structures of these compounds were determined on the basis of spectroscopic analyses, including 1D and 2D NMR, UV, IR and mass spectrometry. The antibacterial activity and cytotoxicity against epidermoid carcinoma of oral cavity (KB) cell line of compounds 1-9 were evaluated.

Monoterpene indole alkaloids from the twigs of Kopsia arborea.

The phytochemistry of Kopsia arborea Blume has received considerable attention, which has resulted in the isolation of a number of new unusual indole alkaloids with intriguing structures. In this study, a new eburnane-type alkaloid, phutdonginin (1), together with eight known alkaloids: 19-OH-(-)- eburnamonine (2), melodinine E (3), kopsinine (4), kopsilongine (5), kopsamine (6), (-)-methylenedioxy-1 1,12-kopsinaline (7), decarbomethoxykopsiline (8), and vincadifformine (9), were isolated from the twigs of K. arborea. Their structures were characterized extensively by 1D and 2D NMR spectroscopy and HR-ESI-MS. All compounds were submitted to TLC screening for acetylcholinesterase inhibitory activities. Only kopsamine and decarbomethoxykopsiline showed AChE inhibition with MIR values of 12.5 and 6.25 µg, respectively, compared with galanthamine (positive control, 0.004 µg). In addition, compounds 1 and 2 inhibited moderate antibacterial activity against E. coli TISTR 780 with the MIC value of 32 .g/mL.

Antibacterial compounds from the roots of Cratoxylumformosum spp. pruniflorum.

Phytochemical investigation of the roots of Cratoxylum formosum spp. pruniflolnnm led to the isolation and identification of a new xanthone, namely cratopruniforone (1), together with 13 known compounds (2-14). Some of these more abundant compounds were evaluated for their antibacterial activities.

Antibacterial tetraoxygenated xanthones from the immature fruits of Garcinia cowa.

A phytochemical investigation of the acetone extract from the immature fruits of Garcinia cowa led to the isolation of two novel tetraoxygenated xanthones, garcicowanones A (1) and B (2), together with eight known tetraoxygeanted xanthones. Their structures were determined by spectroscopic analysis. All isolated compounds were evaluated for their antibacterial activity against Bacillus cereus TISTR 688, Bacillus subtilis TISTR 008, Micrococcus luteus TISTR 884, Staphylococcus aureus TISTR 1466, Escherichia coli TISTR 780, Pseudomonas aeruginosa TISTR 781, Salmonella typhimurium TISTR 292 and Staphylococcus epidermidis ATCC 12228. α-Mangostin showed potent activity (MIC 0.25-1 µg/mL) against three Gram-positive strains and garcicowanone A and ß-mangostin exhibited strong antibacterial activity against B. cereus with the same MIC values of 0.25 µg/mL.

Antibacterial compounds from Glycosmis puberula twigs.

The first phytochemical investigation of Glycosmis puberula twigs led to the isolation and identification of a new quinolone alkaloid, glycosmispuberulone (1), along with ten known compounds (2-11). The structures were elucidated by spectroscopic analyses and comparison with previously reported data. Their antibacterial activities against Gram-positive and Gram-negative bacteria were also evaluated.

Alstoniaphyllines A-C, unusual nitrogenous derivatives from the bark of Alstonia macrophylla.

Chemical investigation of an alkaloidal extract of Alstonia macrophylla bark led to the isolation and identification of two new nitrogenous derivatives, alstoniaphyllines A (1) and B (2), a new indole alkaloid, alstoniaphylline C (4), and eight known alkaloids (3, 5-11). Alstonisine (9) exhibited antiplasmodial activity against Plasmodium falciparum, with an IC50 of 7.6 µM.

Clausenawallines G-K, carbazole alkaloids from Clausena wallichii twigs.

Five carbazole alkaloids, clausenawallines G-K (1-5), along with 12 known alkaloids (6-17) were isolated from the twigs of Clausena wallichii. Their structures were established using spectroscopic methods and the antibacterial activity of compounds 1-5 was evaluated.

Concise synthesis of α-substituted 2-benzofuranmethamines and other 2-subsituted benzofurans via α-substituted 2-benzofuranmethyl carbocation intermediates.

Propargyl amines 4, where R(3) is aryl, undergo 5-exo-dig cyclization reactions under relatively mild conditions (AgNO(3), DMF, 60 °C, 1 h) to give 3-amino-2,3-dihydro-2-arylmethylidenebenzofurans 5 (R(3) = aryl). In contrast, substrates where R(3) is alkyl undergo competing 6-endo-dig and 5-exo-dig cyclization processes. The hydroxymethyl substrate 4 (R(3) = CH(2)OH), however, was smoothly converted to its corresponding 5-exo-dig cyclization product 5, likely due to the assistance of the primary hydroxyl group in the 5-exo-dig cyclization process by silver cation coordination. Under more enforcing conditions (AgNO(3), DMF, 100 °C, 18 h), the initially formed products 5 undergo a 1,3-allylic rearrangement to their corresponding 2-substituted benzofuran derivatives 6. This rearrangement can also be effected by treating 5 with AgNO(3) in DMF at 100 °C for 18 h or BF(3)·Et(2)O at rt. 2-(3-Butenyl)benzofurans 7 (Nu = allyl) can be prepared by treatment of 5 with BF(3)·Et(2)O and allyltributylstannane. Furan and MeOH could also be employed as external nucleophiles in these BF(3)·Et(2)O-promoted reactions.

Benzophenone and xanthone derivatives from the inflorescences of Garcinia cowa.

The purification of the acetone extract from the inflorescences of Garcinia cowa led to the isolation of a new benzophenone derivative, cowanone (1), together with seven known xanthones, α-mangostin (2), ß-mangostin (3), cowanin (4), fuscaxanthone A (5), 9-hydroxycalabaxanthone (6), garcinianone A (7) and cowanol (8). The structures of the isolated compounds were elucidated by analysis of their spectroscopic data including 1D and 2D NMR data. All isolated compounds were evaluated for their antibacterial activities against Staphylococcus aureus (SA) and methicillin-resistant S. aureus (MRSA).

Rearranged benzophenones and prenylated xanthones from Garcinia propinqua twigs.

The first phytochemical investigation of Garcinia propinqua has led to the isolation and identification of three new compounds, including two rearranged benzophenones, doitunggarcinones A (1) and B (2), and a xanthone, doitunggarcinone C (3), together with seven known compounds (4-10). The structures of 1-3 were elucidated on the basis of spectroscopic methods, including UV, IR, NMR, and MS. The antibacterial activity of the 10 isolates was evaluated against Escherichia coli TISTR 780, Salmonella typhimurium TISTR 292, Staphylococcus aureus TISTR 1466, and methicillin-resistant Staphylococcus aureus (MRSA) SK1.

Antibacterial compounds from Zanthoxylum rhetsa.

A new amide, zanthorhetsamide (1), along with nine known compounds (2-10) was isolated from the roots and stem barks of Zanthoxylum rhetsa. The structure was characterized by spectroscopic methods. In addition, the antibacterial activity of the isolates was evaluated. Dihydrochelerythrine (4) exhibited strong activity against methicillin-resistant Staphylococcus aureus SK1 and moderate activity against Escherichia coli TISTR 780 with MIC values of 8 and 16 µg/mL, respectively.