Anuchit Plubrukarn

Acetylcholinesterase-inhibiting activity of pyrrole derivatives from a novel marine gliding bacterium, Rapidithrix thailandica.

Acetylcholinesterase-inhibiting activity of marinoquinoline A (1), a new pyrroloquinoline from a novel species of a marine gliding bacterium Rapidithrix thailandica, was assessed (IC50 4.9 μM). Two related pyrrole derivatives, 3-(2′-aminophenyl)-pyrrole (3) and 2,2-dimethyl-pyrrolo-1,2-dihydroquinoline (4), were also isolated from two other strains of R. thailandica. The isolation of 3 from a natural source is reported here for the first time. Compound 4 was proposed to be an isolation artifact derived from 3. The two isolated compounds were virtually inactive in the acetylcholinesterase-inhibitory assay (enzyme inhibition < 30% at 0.1 g L−1).

Acetylcholinesterase-inhibiting steroidal alkaloid from the sponge Corticium sp.

A new stigmastane-type steroidal alkaloid, 4-acetoxy-plakinamine B (1), was isolated from the Thai sponge Corticium sp. The compound was subjected to the acetylcholinesterase inhibitory activity determination to reveal a high inhibitory activity (IC(50) 3.75+/-1.69 microM). The kinetics of enzyme inhibition showed a decrease in V(max), whereas K(m) was increased, thus suggesting an unusual mixed-competitive mode of inhibition. Compound 1 is the first steroidal alkaloid bearing a stigmastane skeleton ever been reported to exhibit such good potency in the acetylcholinesterase inhibition bioassay.

Anti-inflammatory activity of diterpenes from Croton stellatopilosus on LPS-induced RAW264.7 cells

An acyclic diterpene (plaunotol; 1) and two furanoditerpenes (plaunolide, 2 and plaunol E, 3), were isolated from Croton stellatopilosus leaves, and assessed for their inhibitory activity on nitric oxide (NO) production by lipopolysaccharide (LPS)-induced RAW264.7 cells. Plaunotol, plaunolide and plaunol E exhibited inhibitory activity with IC50 values of 3.41, 17.09 and 2.79xa0μM, respectively. Cytotoxic effects were observed at concentrations of ≥100xa0μM for plaunotol and ≥10xa0μM for plaunol E. In order to understand the mechanism of this anti-inflammatory activity, transcription profiles of the COX-1, COX-2 and iNOS genes were measured using a quantitative RT-PCR technique. The level of gene expression was expressed as a relative quantitation according to the comparative CT method. The results indicated that plaunotol stimulated the COX-1 and COX-2 genes, and suppressed expression of the iNOS gene. Treatment of cells with plaunolide caused a downregulation of the expressions of the COX-1, COX-2 and iNOS genes. In contrast, plaunol E inhibited the expression of the COX-2, stimulated COX-1 and iNOS expressions. In summary, the present study shows that different diterpenes from C. stellatopilosus leaves exhibit anti-inflammatory activity towards LPS-activated RAW264.7 cells by different mechanisms. Our results provide data to support further investigations into the possibility that these diterpenes could be alternatives to act as anti-inflammatory agents.

Kabiramides J and K, trisoxazole macrolides from the sponge Pachastrissa nux.

Three trisoxazole macrolides possessing a 30-α,β-enone moiety, including the known kabiramide G (1) and the new kabiramides J (2) and K (3), were isolated from the sponge Pachastrissa nux, along with the previously reported kabiramides B (4), C (5), and D (6). To date, the enone moiety has been found to associate solely with the trisoxazole macrolides from P. nux. All of the isolated macrolides showed moderate to strong antimalarial and cytotoxic activities, except for 1, which possessed only potent cytotoxicity.

Bridged tricyclic sesquiterpenes from the tubercle nudibranch Phyllidia coelestis Bergh.

A new sesquiterpene, 1-formamido-10(1→2)-abeopupukeanane (1), was isolated from the tubercle nudibranch Phyllidia coelestis Bergh, along with 2-formamidopupukeanane (2), which is reported here as a natural product for the first time. A rearrangement pathway toward the unprecedented tricyclo[4.4.0.0(2,8)]decane skeleton is proposed. Both compounds showed antiproliferative activity when targeting HeLa, MCF-7, KB, and HT-29 cancer cell lines in the range 0.05-10 μM.

Bifunctionalized Amphilectane Diterpenes from the Sponge Stylissa cf. massa

Two new amphilectane-type diterpenes, 8-isocyanato-15-formamidoamphilect-11(20)-ene (1) and 8-isothiocyanato-15-formamidoamphilect-11(20)-ene (2), along with two known derivatives, 8-isocyano-15-formamidoamphilect-11(20)-ene (3) and 7-formamidoamphilect-11(20),15-diene (4), were isolated from the sponge Stylissa cf. massa. Diterpenes bearing two different isonitrile-related functionalities, as in 1-3, are rare. The coexistence of these compounds, all of which possess the identical carbon skeleton, in the same sponge specimen suggests interconversion among them. All the isolated compounds were tested for antimalarial activity. Compound 3 proved approximately 10 times more active than 1 and 2, indicating the importance of the isonitrile moiety to antimalarial activity versus the isocyanate and isothiocyanate groups, respectively. Compound 4, which contains only the formamide group, was inactive at the highest concentration tested.

Kabiramide L, a new antiplasmodial trisoxazole macrolide from the sponge Pachastrissa nux

An extensive search for the trisoxazole macrolides in the Thai specimen of the sponge Pachastrissa nux led to the isolation of a new kabiramide derivative, kabiramide L (1) and the previously reported kabiramide I (2). Both macrolides had a moderate antiplasmodial activity against Plasmodium falciparum K1 with IC50s of 2.6 and 4.5u2009µM, respectively. To date, P. nux has been the only known source of the trisoxazole macrolides bearing the 30-enone moiety. Both compounds were also added to the list of chemicals postulated to play a defensive role in the P. nux sponge.

Structure―activity relationships of antitubercular scalaranes: Heteronemin revisited

A series of heteronemin-related antitubercular scalaranes, both from natural products and from chemical derivatization, were subjected to structure-activity investigations. Based on the activity profile, three main regions; i.e., the substituted groups hovering over C-19/C-18 and furan moiety, the functionalities in the vicinity of C-16 and the right-hand side of ring D, and the substituted groups on C-12, were speculated as the areas influencing the antitubercular activity of the scalaranes. The results suggested the promising possibility for the further investigation towards the modes of actions and/or target sites of the compounds.

Intracolonial Allocation of Trisoxazole Macrolides in the Sponge Pachastrissa nux

Pachastrissa nux has two distinctive growth forms in one colony, i.e., the protruding gorgonian‐shaped capitum and the substratum‐attached irregular‐shaped base. The sponge has the ability to allocate specifically its major secondary metabolites to the two parts in different levels. Using two cytotoxic trisoxazole macrolides, kabiramides C (2) and G (3), as chemical markers, it was found that the capitum accumulated higher contents of either or both compounds than did the base. However, there were neither inductive nor suppressive correlations among the allocation profiles of either compound in either part of the sponge. The allocation of kabiramides was a trade‐off with the structural materials involved in reinforcing the strength of the sponge. To date, this is the second report that provides evidence of the specific allocation of bioactive metabolites in two distinctively different organ‐like structures in a single sponge colony.

Cytotoxic Isoquinoline Quinones from the Thai Sponge Cribrochalina

Three isoquinoline quinones, (+)– N -formyl-1,2-dihydrorenierone (1), O -demethylrenierone (2), and mimosamycin (3), were isolated from the Thai purplish-blue sponge, Cribrochalina sp. The cytotoxicity against various cancer cell lines of the three compounds, determined employing the SRB method, was first reported here. It was found that all three were highly active, especially against MCF-7 breast carcinoma and HeLa cervical cancer cell lines. Also, this report is the first isolation of (+)-enantiomer of N -formyl-1,2-dihydrorenierone from a naturally occurring source.