Two new farnesyl hydroquinones from Pestalotiopsis diploclisia (BCC 35283), the fungus associated with algae.

Two new hydroquinones bearing a 1,3-enyne moiety, pestalotioquinols G and H, together with four known compounds, including pestalotioquinol A, phomonitroester, (R)-4,6,8-trihydroxy-3,4-dihydronaphthalen-1(2H)-one, and scylatone were isolated from the marine fungus Pestalotiopsis diploclisia (BCC 35283). The structures of these compounds were elucidated by analysis of 2D-NMR and HR-MS data. The known pestalotioquinol A displayed antimalarial activity against Plasmodium falciparum K1 with an IC50 value of 19.0 µM, while pestalotioquinol G displayed weak cytotoxic activity against Vero cell lines with an IC50 value of 47.9 µM.

Xanthones from a lignicolous freshwater fungus (BCC 28210).

Four xanthones (1‒4) and a known compound, mansonone D (5), were isolated from the lignicolous freshwater fungus BCC 28210 (family, Chaetosphaeriaceae). The structures of these compounds were elucidated by extensive spectroscopic analysis. Among the isolated metabolites, compound 2 and the known mansonone D (5) displayed antimalarial activity against Plasmodium falciparum K1 with IC50 values of 7.75 and 0.55 µg/mL, respectively. Compound 4 displayed antibacterial activity against Bacillus cereus with an MIC value of 6.25 µg/mL.

Salicylaldehyde and dihydroisobenzofuran derivatives from the marine fungus Zopfiella marina.

Two salicylaldehyde derivatives (1 and 2), a hydroxymethylphenol (3), five dihydroisobenzofuran (4-8) derivatives, and a 5-chloro-3-deoxyisoochracinic acid (9), together with a known 3-deoxyisoochracinic acid (10) were isolated from the marine fungus Zopfiella marina BCC 18240 (or NBRC 30420). The structures of these compounds were elucidated by extensive spectroscopic analysis. Compound 1 showed weak antituberculous activity against Mycobacterium tuberculosis H37Ra, and antibacterial activity against Bacillus cereus with MIC values of 25 and 12.5 µg/mL, respectively.

Cadinane sesquiterpenoids from the basidiomycete Stereum cf. sanguinolentum BCC 22926.

Stereumins Q-U, together with known stereumins A, B, K, L, and N, as well as ent-strobilols E and G were isolated from the culture of Stereum cf. sanguinolentum BCC 22926. Their structures were elucidated by extensive spectroscopic analyses. The absolute configurations of stereumins A and Q, as well as ent-strobilol E were established by application of the modified Mosher's method. Stereumin T displayed antibacterial activity against Bacilluscereus with a MIC value of 3.97µM.

Antiangiogenic effect of chamigrane endoperoxides from a Thai mangrove-derived fungus.

As part of our ongoing efforts to investigate natural products with potential for use as cancer treatments, we have recently disclosed the cytotoxicity of unique nor-chamigrane (1) and chamigrane (2, 3) endoperoxides from a Thai mangrove-derived fungus. Reinvestigation of this fungus in a large-scale fermentation led to the isolation of an additional new chamigrane endoperoxide (4) and one known analogue (5). Among these isolated metabolites, compound 3 (merulin C) exhibited potent antiangiogenic activity mainly by suppression of endothelial cell proliferation and migration in a dose-dependent manner, and its effect is mediated by reduction in the phosphorylation of Erk1/2. Merulin C also displayed promising activity in a rat aortic ring sprouting (ex vivo) and a mouse Matrigel (in vivo) assay.

Cytotoxic nor-chamigrane and chamigrane endoperoxides from a basidiomycetous fungus.

A new nor-chamigrane endoperoxide, merulin A (1), and two new chamigrane endoperoxides, merulins B and C (2, 3), were isolated from the culture broth extract of an endophytic fungus of Xylocarpus granatum. Their structures were elucidated on the basis of spectroscopic, mainly NMR and MS, data. X-ray crystallographic analysis confirmed the structure of 1. Compounds 1 and 3 displayed significant cytotoxicity against human breast (BT474) and colon (SW620) cancer cell lines.

Oblongolides from the endophytic fungus Phomopsis sp. BCC 9789.

Six new oblongolides, W1, W2, X, Y, and Z (1-3, 6, 7) and 2-deoxy-4alpha-hydroxyoblongolide X (4), and the known compounds oblongolide (8), oblongolides T, C, and Q (5, 9, 10), and (-)-5-methylmellein were isolated from the endophytic fungus Phomopsis sp. BCC 9789. Compound 7 showed anti-HSV-1 activity (IC50=14 microM) and cytotoxic activities against KB, BC, NCI-H187, and nonmalignant (Vero) cell lines with respective IC50 values of 37, 26, 32, and 60 microM. Cytotoxic activity against the BC cell line was also observed for compound 6, with an IC50 value of 48 microM.

Isariotins E and F, spirocyclic and bicyclic hemiacetals from the entomopathogenic fungus Isaria tenuipes BCC 12625.

New spirocyclic and bicyclic hemiacetals, isariotins E (1) and F (2), together with TK-57-164A (3) were isolated from the entomopathogenic fungus Isaria tenuipes BCC 12625. The absolute configuration of 3 was addressed by application of the modified Mosher's method. Isariotin F (2) exhibited activity against the malaria parasite Plasmodium falciparum K1 with an IC(50) value of 5.1 microM and cytotoxic activities against cancer cell lines (KB, BC, and NCI-H187) and nonmalignant (Vero) cells with respective IC(50) values of 15.8, 2.4, 1.6, and 2.9 microM.

Phenolic glycosides from the filamentous fungus Acremonium sp. BCC 14080.

New phenolic mono- and digalactopyranosides (1 and 2), their aglycone KS-501a (3), and a new phenolic 4-O-methylglucopyranoside (4) were isolated from the filamentous fungus Acremonium sp. BCC 14080. Structures of these compounds were elucidated by extensive MS and NMR spectroscopic analyses. Compound 1 displayed anti-HSV-1 activity with an IC(50) value of 7.2 microM. Compound 3 exhibited activity against Plasmodium falciparum K1 with an IC(50) value of 9.9 microM.

New diphenyl ethers from the insect pathogenic fungus Cordyceps sp. BCC 1861.

Two novel diphenyl ether glycosides and a new diphenyl ether, cordyol A-C (1-3), were isolated from the insect pathogenic fungus Cordyceps sp. BCC 1861. Structures of these compounds were elucidated by NMR and MS spectral analyses. Cordyol C (3) exhibited significant anti-HSV-1 activity with an IC50 value of 1.3 microg/ml, and cytotoxic activity against BC and NCI-H187 cancer cell lines with IC50 values of 8.65 and 3.72 microg/ml, respectively. Cordyol A (1) displayed weak antimycobacterial activity with a MIC value of 100 microg/ml.

Menisporopsin B, a new polyester from the seed fungus Menisporopsis theobromae BCC 4162.

A new linear polyester, menisporopsin B, along with the known macrocyclic polyester, menisporopsin A, was isolated from the seed fungus Menisporopsis theobromae BCC 4162. The structure of menisposopsin B was addressed primarily by spectroscopic analyses, and the stereochemistry was established by chemical correlation. Menisporopsin B exhibited antimalarial activity with an IC(50) value of 1.0 microg/ml.

Dynamic combinatorial carbohydrate libraries: probing the binding site of the concanavalin A lectin.

Dynamic combinatorial chemistry (DCC) has emerged as an efficient approach to receptor/ligand identification based on the generation of combinatorial libraries by reversible interconversion of the library constituents. In this study, the implementation of such libraries on carbohydrate-lectin interactions was examined with the plant lectin Concanavalin A as a target species. Dynamic carbohydrate libraries were generated from a pool of carbohydrate aldehydes and hydrazide linker/scaffold components through reversible acylhydrazone exchange, resulting in libraries containing up to 474 constituents. Dynamic deconvolution allowed the efficient identification of the structural features required for binding to Concanavalin A and the selection of a strong binder, a tritopic mannoside, showing an IC(50)-value of 22 microM.

Generation of bis-cationic heterocyclic inhibitors of Bacillus subtilis HPr kinase/phosphatase from a ditopic dynamic combinatorial library.

Ditopic dynamic combinatorial libraries were generated and screened toward inhibition of the bifunctional enzyme HPr kinase/phosphatase from Bacillus subtilis. The libraries were composed of all possible combinations resulting from the dynamic interconversion of 16 hydrazides and five monoaldehyde or dialdehyde building blocks, resulting in libraries containing up to 440 different constituents. Of all possible acyl hydrazones formed, active compounds containing two terminal cationic heterocyclic recognition groups separated by a spacer of appropriate structure could be rapidly identified using a dynamic deconvolution procedure. Thus, parallel testing of sublibraries where one specific component was excluded basically revealed all the essential components. A potent ditopic inhibitor, based on 2-aminobenzimidazole, was identified from the process.

Chemical biology of dynamic combinatorial libraries.

Dynamic combinatorial chemistry (DCC) is a recently introduced supramolecular approach to generate libraries of chemical compounds based on reversible exchange processes. The building elements are spontaneously and reversibly assembled to virtually encompass all possible combinations, allowing for simple one-step generation of complex libraries. The method has been applied to a variety of combinatorial systems, ranging from synthetic models to materials science and drug discovery, and enables the establishment of adaptive processes due to the dynamic interchange of the library constituents and its evolution toward the best fit to the target. In particular, it has the potential to become a useful tool in the direct screening of ligands to a chosen receptor without extensive prior knowledge of the site structure, and several biological systems have been targeted. In the vast field of glycoscience, the concept may find special perspective in response to the highly complex nature of carbohydrate-protein interactions. This chapter summarises studies that have been performed using DCC in biological systems, with special emphasis on glycoscience.