Brasilicardin A, a natural immunosuppressant, targets amino Acid transport system L.

Lymphocytes in T cell activation require extracellular nutrients to provide energy for cellular proliferation and effector functions. Therefore, inhibitors of nutrient transporters are expected to be a new class of immunosuppressant. Here, we report that the molecular target of brasilicardin A (BraA), an immunosuppressive compound, is the amino acid transporter system L.

Cladionol A, a polyketide glycoside from marine-derived fungus Gliocladium species.

A new polyketide glycoside, cladionol A (1), was isolated from the cultured broth of a fungus Gliocladium sp., which was separated from sea grass Syringodium isoetifolium, and the structure was elucidated by spectroscopic data. The relative stereochemistry of C-2-C-3 was assigned by mainly J-based configuration analysis, while those of two sugar units were elucidated to be beta-mannopyranoside and arabitol on the basis of NOESY data and/or 1H-1H couplings.

Scalusamides A-C, new pyrrolidine alkaloids from the marine-derived fungus Penicillium citrinum.

Three new pyrrolidine alkaloids, scalusamides A-C (1-3), were isolated from the cultured broth of the fungus Penicillium citrinum, which was separated from the gastrointestine of a marine fish, and the structures were elucidated by spectroscopic data. The absolute stereochemistry of C-2 in the pyrrolidine unit was determined by HPLC analysis of a Marfey's derivative of the hydrolysate of 1, while that of 2 and 3 was assigned by comparison of spectroscopic data of 3 and reductive products of 1 and 2. On the other hand, each of 1-3 was found to be a mixture of epimers at C-7.

SAR studies of brasilicardin A for immunosuppressive and cytotoxic activities.

Eleven derivatives (5-13, 15, and 16) of an immunosuppressive and cytotoxic tricyclic terpenoid, brasilicardin A (1), were prepared and assayed for inhibitory effects to the mouse mixed lymphocyte reaction (MLR) and seven human tumor cell lines. The 17N-methyl form (8) of 1 showed the most potent immunosuppressive activity in mouse MLR, while induction of more bulky group for N-17 resulted in significant decrease of the activity. Compound 8 also showed potent cytotoxic activity against DLD-1, Lu-65, A549, K562, and MOLT-4 cells, while the benzyl ester (13) of 1 exhibited potent cytotoxicity against K562, MOLT-4, and jarkat leukemia cell lines.

Brasilicardins B-D, new tricyclic terpenoids [correction of terpernoids] from actinomycete Nocardia brasiliensis.

Three new tricyclic terpenoids, brasilicardins B-D (2-4), were isolated together with brasilicardin A (1), a potent immunosuppressive compound, from the cultured broth of a pathogenic actinomycete Nocardia brasiliensis IFM0406, and the structures and stereochemistry were determined by spectroscopic data and a single crystal X-ray diffraction analysis. The immunosuppressive and cytotoxic activities of 2-4 were examined in the comparison with 1.

Citrinadin A, a novel pentacyclic alkaloid from marine-derived fungus Penicillium citrinum.

[structure: see text] A novel pentacyclic alkaloid, citrinadin A (1), was isolated from the cultured broth of the fungus Penicillium citrinum, which was separated from a marine red alga, and the structure was elucidated by spectroscopic data. The relative stereochemistry of the pentacyclic core was assigned on the basis of NOESY data and (1)H-(1)H coupling constants, and the presence of an N,N-dimethyl-L-valine residue in 1 was determined by chiral HPLC analysis of the hydrolysate.

Absolute stereochemistry of immunosuppressive macrolide brasilinolide A and its new congener brasilinolide C.

Brasilinolide A (2) is a 32-membered polyhydroxyl macrolide with immunosuppressive activity isolated from a pathogenic actinomycete, Nocardia brasiliensis IFM0406. The absolute configurations at 26 chiral centers of 2 and its new congener, brasilinolide C (1), were determined on the basis of the spectral data of 1 and degradation products derived from 1 and 2.

Modiolides A and B, two new 10-membered macrolides from a marine-derived fungus.

Two new 10-membered macrolides, modiolides A (1) and B (2), and a new linear pentaketide, modiolin (3), were isolated from the cultured broth of a fungus Paraphaeosphaeria sp. (N-119), which was separated from a marine horse mussel, and the structures were elucidated by spectroscopic data.