Two antibacterial and PPARα/γ-agonistic unsaturated keto fatty acids from a coral-associated actinomycete of the genus Micrococcus

• Amit Raj Sharma,
• Enjuro Harunari,
• Naoya Oku,
• Nobuyasu Matsuura,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 297–304, doi:10.3762/bjoc.16.29

• ; Micrococcus; PPAR; Introduction Marine actinobacteria are considered as a potential source for novel natural products with high structural diversity, unique biological activity, and molecular modes of action beneficial to drug development [1][2][3]. Actinobacteria in marine environments are mostly found in

• cytotoxicity against murine leukemia P388 cells at 100 µM. Additionally, compounds 1 and 2 were evaluated for agonist activity to peroxisome proliferator-activated receptors (PPARs) because similar oxo fatty acids are known to act as PPAR agonists [42]. PPARs are ligand-activated transcription factors playing

• physiological functions in energy metabolism, PPARs are the molecular targets of metabolic disorders [48]. To assess the PPAR isoform specificity of 1 and 2, three reporter cell lines expressing luciferase genes in response to PPARα, PPARβ/δ, and PPARγ agonists were used [49]. The agonist activity was

ADDP and PS-PPh₃: an efficient Mitsunobu protocol for the preparation of pyridine ether PPAR agonists

• Paul S. Humphries,
• Quyen-Quyen T. Do and
• David M. Wilhite

Beilstein J. Org. Chem. 2006, 2, No. 21, doi:10.1186/1860-5397-2-21

• Paul S. Humphries Quyen-Quyen T. Do David M. Wilhite Pfizer Global R&D, Department of Medicinal Chemistry, 10614 Science Center Drive, San Diego, CA 92121, USA 10.1186/1860-5397-2-21 Abstract A series of pyridine ether PPAR agonists were synthesized through an ADDP and PS-PPh3 modified Mitsunobu

• pathways for lipid handling, insulin sensitivity, inflammation and other functions have led to marketed drugs and vast clinical and preclinical research efforts.[1][2][3][4][5][6][7][8][9][10][11] In 1991, a series of PPAR analogues were disclosed, which for the first time did not contain a thiazolidine

• -2,4-dione pharmacophore.[12] These were propanoic acid derivatives with α-substitution to collectively serve as a mimic for the thiazolidine-2,4-dione ring. Based on the above and a knowledge of PPAR ligands publicly disclosed, we wished to synthesize compounds represented by the general structure 1