Flavanones, a class of flavonoids, are abundant in fruits, vegetables, and herbs. They are known to have several biological activities, such as anti-inflammatory and anti-cancer activities, but their effects on obesity remain unclear. Obesity is closely associated with adipocyte differentiation and lipid accumulation in adipose tissue. Therefore, in this study, we examined the effects of flavanone derivatives on adipocyte differentiation and lipid accumulation by using 3T3-L1 cells. Among the 15 flavanone derivatives studied, 4′-phenylflavanone (4PF), with a biphenyl structure, significantly inhibited adipocyte differentiation-related lipid accumulation in 3T3-L1 cells; this inhibition of lipid accumulation was dose-dependent. Gene expression analysis showed that 4PF suppressed the expression of adipogenic marker genes. Although the induction of peroxisome proliferator activator γ2 (Pparγ2), a master regulator of adipocyte differentiation, and its target genes during adipocyte differentiation was attenuated in 4PF-treated cells, 4PF did not directly regulate Pparγ2 gene expression and its activation. In contrast, 4PF suppressed mitotic clonal expansion (MCE), which is associated with changes in the expression of proliferation-related genes at the early stages of adipocyte differentiation. Taken together, these results suggest that 4PF inhibits lipid accumulation because it suppresses MCE during adipocyte differentiation. Thus, our findings may help in the development of anti-obesity drugs.

Background/Objectives: Linezolid is a first-in-class oxazolidinone antibiotic that exhibits activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. However, its clinical use is often restricted because of hematological toxicities, particularly thrombocytopenia, in patients with renal impairment. That side effect is thought to result from the systemic accumulation of pharmacologically inactive metabolites generated by oxidative degradation and ring-opening of the morpholine, but the details remain unclear. In this study, we established a novel synthetic route for four linezolid metabolites (PNU-142618, 142300, 142586 and 173558). Methods: The four major metabolites, which are secondary or tertiary amines, were synthesized using the aniline derivatives protected with a 2-nitrobenzensulfonyl (Ns) group. Results: Application of this Ns strategy enabled selective N-alkylation, enabling efficient synthesis of the target metabolites. The desired metabolites containing a carboxylic acid group were obtained as their sodium salts. This is the first report on the synthesis of PNU-142618 and 173558. Conclusions: The established synthetic pathway provides access to four linezolid metabolites. The results facilitated the provision of compounds necessary for comprehensive pharmacokinetic and toxicological studies.