Hypothemycin-Type Resorcylic Acid Lactones with Immunosuppressive Activities from a Podospora sp.

Abstract

Twelve new hypothemycin-type resorcylic acid lactones, three 10-membered (1−3) and nine 14-membered (4− 12), together with seven known analogues (13−19), were obtained from the solid rice-based culture of Podospora sp. G214. Their structures were elucidated utilizing spectroscopic analysis, and the absolute configurations were determined by modified Mosher's method, Mo 2 (OAc) 4 -induced electronic circular dichroism experiments, and single-crystal X-ray diffraction. Compounds 1, 5, 10, and 12−19 exhibited potent immunosuppressive activities against concanavalin A-induced T cell proliferation with IC 50 values ranging from 6.0 to 25.1 μM and lipopolysaccharide-induced B cell proliferation with IC 50 values ranging from 6.2 to 29.1 μM. Further studies revealed that 1 induced apoptosis in activated T cells through the JNK-mediated mitochondrial pathway.

Natural ten-membered lactones: sources, structural diversity, biological activity, and intriguing future

“…The endophytic fungus Cytospora sp. is a producer of a large family of TMLs called cytospolides A-P (34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49). This family has one chemical feature that is unique for fungal TMLsthe presence of a methyl group at C-2.…”

“…3 In contrast, there are practically no targeted studies on SAR analysis for other types of activity. For example, Lu et al (2011) 26,27 discussed the possible SAR of cytospolides (34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49) and stated that the conguration of C-2 is important for cytotoxic activity. Among the family of bellidisins (27,28,50) and co-isolated compounds from Phoma bellidis, the 4S,5S-4,5-epoxyhexenoyl group in the ester moiety of bellidisin D ( 28) is probably the key pharmacophore for its cytotoxicity.…”

“…Further studies have revealed that compound 69 induces apoptosis in activated T cells through the JNK-mediated mitochondrial pathway. 49 Two new RALs, sumalactones A ( 72 ) and B ( 73 ), were isolated from the marine fungus Penicillium sumatrense , along with four curvularin-type macrolides. These compounds were tested for their inhibitory activities against LPS-induced NO production in RAW 264.7 macrophages, but they were not active.…”

Meroterpenoids with Potent Immunosuppressive Activity from Fungus Bipolaris zeicola

“…[ 1 ] Since cyclosporine A was demonstrated to be effective for preventing the organ‐graft rejection in 1978, many representative natural immunosuppressive drugs, e.g ., tacrolimus, mycophenolic acid, and rapamycin, have been developed from microbial natural products. [ 2‐3 ] However, these widely used immunosuppressive drugs showed undesirable side effects, such as liver toxicity and renal injury, [ 4 ] giving rise to urgent need for alternatives with high efficacy and low toxicity.…”

Three new pyrrole alkaloids from the endophytic fungus Albifimbria viridis

“…Autoimmune diseases arise when the immune system fails to distinguish between self and non-self [ 1 , 2 ]. Immunosuppressants are often used to prevent and treat the immune rejection of organs and tissues of transplant patients and play an important role in the treatment of various autoimmune diseases [ 3 – 8 ]. Nevertheless, some common immunomodulatory drugs such as mycophenolate mofetil (MMF) and cyclosporin A (CsA) have low efficacy, toxicity, and serious side effects in transplant patients [ 9 – 12 ].…”