Somdej Kanokmedhakul

Cytotoxic pentacyclic and tetracyclic aromatic sesquiterpenes from Phomopsis archeri.

Three new sesquiterpenes, named phomoarcherins A-C (1-3), and four known compounds, kampanol A (4), R-mevalonolactone, ergosterol, and ergosterol peroxide, were isolated from the endophytic fungus Phomopsis archeri. These structures were established on the basis of spectroscopic evidence. The structure and absolute configuration of 1 were confirmed by X-ray crystallographic analysis of its p-bromobenzoate derivative (1a). Compounds 1-4 showed cytotoxicity against five cholangiocarcinoma cell lines (0.1-19.6 μg/mL), while 1 and 2 exhibited weak cytotoxicity against the KB cell line with IC(50) values of 42.1 and 9.4 μg/mL, respectively. In addition, compound 2 showed antimalarial activity against Plasmodium falciparum with an IC(50) value of 0.79 μg/mL.

Antiplasmodial triterpenes from twigs of Gardenia saxatilis.

Ten triterpenes (1-10) were isolated and identified from the twigs of Gardenia saxatilis (Rubiaceae) and were subjected to antiplasmodial evaluation against the parasite Plasmodium falciparum. The first six compounds, lupenone (1), lupeol (2), betulinic acid (3), oleanolic acid (4), ursolic acid (5), and winchic acid (27-O-feruloyloxybetulinic acid) (6) were inactive in the assay. The other four compounds, messagenic acid A (7) and messagenic acid B (8), the 27-O-p-(Z)- and 27-O-p-(E)-coumarate esters of betulinic acid, and a mixture of uncarinic acid E (27-O-p-(E)-coumaroyloxyoleanolic acid) (9) and 27-O-p-(E)-coumaroyloxyursolic acid (10) exhibited antiplasmodial activity, with the IC50 values of 1.5, 3.8 and 2.9 microg/ml, respectively. The results indicated that the p-coumarate moieties at the 27-position, both the cis and trans isomers, contributed to antiplasmodial activity. Introduction of a methoxyl group to the 3-position of the p-coumarate moiety to give a ferulate moiety resulted in loss of activity.

Antimalarial and cytotoxic depsidones from the fungus Chaetomium brasiliense.

Four new depsidones, mollicellins K-N (1-4), and six known depsidones, mollicellins B (5), C (6), E (7), F (8), H (9), and J (10), along with two known sterols were isolated from the fungus Chaetomium brasiliense. Their structures were elucidated on the basis of 1D and 2D NMR spectroscopic data and chemical transformation. Among these isolates, 1-3, 5-7, and 10 exhibited antimalarial activity against Plasmodium falciparum. Only 1 exhibited antimycobacterial activity against Mycobacterium tuberculosis and antifungal activity against Candida albicans using in vitro assays. In addition, 1-10 showed cytotoxicity against the KB, BC1, NCI-H187, and five cholangiocarcinoma cell lines.

Bioactive styryllactones and alkaloid from flowers of Goniothalamus laoticus

ETHNOPHARMACOLOGICAL RELEVANCE Goniothalamus laoticus (Annonaceae) is being used traditionally as a tonic and a febrifuge by the local people in the northeastern part of Thailand. AIM OF STUDY To investigate the Thai medicinal plant, Goniothalamus laoticus, for antiplasmodial, antimycobacterial and cytotoxicity activities. MATERIALS AND METHODS The flowers extracts of Goniothalamus laoticus were isolated by chromatographic techniques. Structures of isolated compounds were identified by spectroscopic methods. The antiplasmodial, antimycobacterial and cytotoxicity evaluation of styryllactone derivatives and alkaloid were also performed. RESULTS Ten compounds, cinnamic acid (1); dihydrochrysine (2); beta-sitosterol (3); six styryllactones, (+)-3-acetylaltholactone (4), goniotriol (5), (+)-altholactone (6), (+)-goniofufurone (7), 9-deoxygoniopypyrone (8), howiinin A (9); and an aporphine alkaloid; (-)-nordicentrine (10) were isolated from flowers of Goniothalamus laoticus. Among these, compounds 1, 3-5, 8-10 are first isolated from the Goniothalamus laoticus. Besides, compound 10 is the first report from the Goniothalamus genus. The isolated compounds were evaluated in antiplasmodial, antimycobacterial and anticancer cell lines tests. Compounds 4-6 and 10 exhibited antiplasmodial activity against Plasmodium falciparum (IC(50) 2.6, 7.9, 2.6 and 0.3 microg/mL, respectively), while 5, 6, 9 and 10 showed antimycobacterial activity against Mycobacterium tuberculosis (MIC 100, 6.25, 6.25 and 12.5 microg/mL, respectively). In addition, compounds 4-10 showed cytotoxicity against cancer cells, KB, BC1, NCI-H187, and MCF-7 with IC(50) ranging from 0.4 to 22.7 microg/mL. CONCLUSION This finding showed that the styryllactone derivatives and alkaloid isolated from the flowers of Goniothalamus laoticus exhibited antiplasmodial activity against Plasmodium falciparum, antimycobacterail against Mycobacterium tuberculosis and cytotoxicity against four cancer cell lines.

Prenylxanthones and a Bicyclo[3.3.1]nona-2,6-diene Derivative from the Fungus Emericella rugulosa

Five new prenylxanthones, ruguloxanthones A-C (1-3), 14-methoxytajixanthone (4), and tajixanthone ethanoate (5), a new bicyclo[3.3.1]nona-2,6-diene derivative, rugulosone (6), and seven known compounds, shamixanthone, tajixanthone, 14-methoxytajixanthone-25-acetate, tajixanthone hydrate, tajixanthone methanoate, isoemericellin, and ergosterol, were isolated from the fungus Emericella rugulosa. The structures of 1-6 were established using spectroscopic techniques. Compound 6 exhibited antimalarial and antimycobacterial activities, as well as cytotoxicity against three cancer cell lines.

Polyacetylenes from the roots of Polyalthia debilis.

Six new linear polyacetylenic C25 and C27 acetogenins (1-6), named debilisones A-F, have been isolated from a methanol extract of roots of Polyalthia debilis. Structures of these compounds were determined by spectroscopic techniques. The absolute configuration at C-17 of 2 was assigned by the modified Moshers method. Compounds 2, 3, and 5 exhibited moderate antimycobacterial activity against Mycobacterium tuberculosis with MIC values of 25.0, 12.5, and 25.0 microg/mL, respectively.

Cytotoxic 10-(indol-3-yl)-[13]cytochalasans from the fungus Chaetomium elatum ChE01.

Nine 10-(indol-3-yl)-[13]cytochalasans such as a new chaetoglobosin V (1); two new natural products, prochaetoglobosin III (2) and prochaetoglobosin IIIed (3); six known chaetoglobosins B-D (4–6), F (7), and G (8) and isochaetoglobosin D (9) in addition to two known sterols, 24(R)-5α,8α-epidioxyergosta-6–22-diene-3β-ol (10) and ergosterol (11), were isolated from the fungus Chaetomium elatum ChE01. The structures of these compounds were elucidated by spectroscopic methods. Compounds 1–9 showed cytotoxicity against the human breast cancer (IC50 2.54–21.29 μM) and cholangiocarcinoma cell lines (IC50 3.41–86.95 μM).

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).

Cytotoxic lasiodiplodin derivatives from the fungus Syncephalastrum racemosum

Chemical investigation of fungal biomass of the fungus Syncephalastrum racemosum led to the isolation of new natural products (3R),(5S)-5-hydroxy-de-O-methyllasiodiplodin (1), 6-oxode-O-methyllasiodiplodin (2), in addition to five known compounds, de-O-methyllasiodiplodin (3), lasiodiplodin (4), (3R),(5R)-5-hydroxy-de-O-methyllasiodiplodin (5), ergosterol (6), and ergosterol peroxide (7). Their structures were elucidated by spectroscopic techniques. The absolute configuration of 1 was determined by a modified Mosher’s method. Compound 1 showed cytotoxicity against cholangiocarcinoma, KKU-M139, KKU-M156, and KKU-M213 cell lines with IC50 values in the range of 14–19 μg/mL, while 3 showed cytotoxicity against KB, BC1, and NCI-H187 cell lines with IC50 values of 12.67, 9.65, and 11.07 μg/mL, respectively.

Cytotoxic and antimalarial azaphilones from Chaetomium longirostre.

Four new azaphilones named longirostrerones A-D (1-4) and three known sterols, ergosteryl palmitate, ergosterol, and ergosterol peroxide, have been isolated from ethyl acetate extract of the fungus Chaetomium longirostre. These structures were determined by 1D and 2D NMR, IR, UV, MS, and CD spectroscopy. Compounds 1-4 exhibited strong cytotoxicity against KB cancer cell lines (IC(50) 0.23-6.38 μM), while only 1 showed potent cytotoxicity against MCF7 and NCI-H187 cell lines (IC50 0.24 and 3.08 μM, respectively). In addition, 1-3 showed antimalarial activity against Plasmodium falciparum (IC50 0.62-3.73 μM).