Schiff bases derived from 3-acetyl-4-hydroxycoumarin represent a promising yet underexplored scaffold in medicinal chemistry. Here, we report the efficient synthesis of a series of bisimine derivative Show more
Schiff bases derived from 3-acetyl-4-hydroxycoumarin represent a promising yet underexplored scaffold in medicinal chemistry. Here, we report the efficient synthesis of a series of bisimine derivatives (3a-j) through condensation with structurally diverse amines, achieving yields of 68-95%. Spectroscopic characterization (NMR, IR, MS) confirmed their unique architectures, with 3j emerging as a standout candidate exhibiting anticancer activity comparable to doxorubicin but with superior selectivity against MCF-7 and A549 cell lines. Among the tested derivatives, compound 3a exhibited the most potent antibacterial activity, with the lowest MIC values observed against Gram-positive strains. Notably, 3f (a thiourea analog) demonstrated broad-spectrum antifungal efficacy (MICs: 1.95-31.25 µg/mL), while 3c surpassed ascorbic acid in radical scavenging (96.7% DPPH inhibition). Molecular docking revealed robust interactions between lead compounds (3b, 3c, 3j) and key therapeutic targets (FGFR1, cIAP1-BIR3), suggesting a dual inhibitory mechanism. These findings underscore the potential of coumarin bisimines as versatile platforms for addressing antibiotic resistance and oxidative stress-related pathologies. Show less
Satellite cells (SCs) are stem cells that mediate skeletal muscle growth and regeneration. Here, we observe that adult quiescent SCs and their activated descendants expressed the homeodomain transcrip Show more
Satellite cells (SCs) are stem cells that mediate skeletal muscle growth and regeneration. Here, we observe that adult quiescent SCs and their activated descendants expressed the homeodomain transcription factor Six1. Genetic disruption of Six1 specifically in adult SCs impaired myogenic cell differentiation, impaired myofiber repair during regeneration, and perturbed homeostasis of the stem cell niche, as indicated by an increase in SC self-renewal. Six1 regulated the expression of the myogenic regulatory factors MyoD and Myogenin, but not Myf5, which suggests that Six1 acts on divergent genetic networks in the embryo and in the adult. Moreover, we demonstrate that Six1 regulates the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway during regeneration via direct control of Dusp6 transcription. Muscles lacking Dusp6 were able to regenerate properly but showed a marked increase in SC number after regeneration. We conclude that Six1 homeoproteins act as a rheostat system to ensure proper regeneration of the tissue and replenishment of the stem cell pool during the events that follow skeletal muscle trauma. Show less