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Resorcylic acid lactones from a Podospora sp. that induce apoptosis in activated T cells through MAPKs/AKT pathway.
- Source :
-
Bioorganic chemistry [Bioorg Chem] 2022 Jan; Vol. 118, pp. 105482. Date of Electronic Publication: 2021 Nov 11. - Publication Year :
- 2022
-
Abstract
- Podomycins A-L (1-12), 12 undescribed hypothemycin-type resorcylic acid lactones (RALs), were characterized from Podospora sp. G214, an endophyte harbored in the roots of Sanguisorba officinalis L. Their structures were addressed by spectroscopic data, X-ray crystallography, the modified Mosher's method, together with Mo <subscript>2</subscript> (OAc) <subscript>4</subscript> - and Rh <subscript>2</subscript> (OCOCF <subscript>3</subscript> ) <subscript>4</subscript> -induced electronic circular dichroism (ICD) experiments. Podomycins A-C (1-3) represent the first class of natural RALs with a 13-membered macrolactone ring, while 4-12 are rearranged methoxycarbonyl substituted RALs. Biologically, compounds 2, 6, 8, 10, and 12 displayed immunosuppressive activities against T cell proliferation with IC <subscript>50</subscript> values of 14.5-21.9 μM, and B cell proliferation with IC <subscript>50</subscript> values of 22.3-36.5 μM, respectively. Further mechanism of action research demonstrated that podomycin F (6) distinctly induced apoptosis in activated T cells via MAPKs/AKT pathway.<br /> (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
B-Lymphocytes drug effects
B-Lymphocytes metabolism
Cell Proliferation drug effects
Dose-Response Relationship, Drug
Immunosuppressive Agents chemistry
Immunosuppressive Agents isolation & purification
Lactones chemistry
Lactones isolation & purification
MAP Kinase Signaling System
Male
Mice
Mice, Inbred BALB C
Molecular Structure
Proto-Oncogene Proteins c-akt
Structure-Activity Relationship
T-Lymphocytes metabolism
Apoptosis drug effects
Immunosuppressive Agents pharmacology
Lactones pharmacology
Podospora chemistry
T-Lymphocytes drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2120
- Volume :
- 118
- Database :
- MEDLINE
- Journal :
- Bioorganic chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 34801946
- Full Text :
- https://doi.org/10.1016/j.bioorg.2021.105482