Fused oxazepine-naphthoquinones as novel cytotoxic agents with diverse modes of action in yeast.

The naphthoquinone moiety is commonly found in numerous natural cytotoxic compounds with diverse and pleiotropic modes of action (MOAs). The moiety can exist as a standalone pharmacophore or combined with other pharmacophores to enrich their MOAs. Here, we report that the synthetic fusion of naphthoquinones and oxazepines provides potent cytotoxic compounds with diverse MOAs.

Dorsal root ganglion inflammation by oxaliplatin toxicity: DPEP1 as possible target for peripheral neuropathy prevention.

Background: Peripheral neuropathy (PN) constitutes a dose-limiting side effect of oxaliplatin chemotherapy that often compromises the efficacy of antineoplastic treatments. Sensory neurons damage in dorsal root ganglia (DRG) are the cellular substrate of PN complex molecular origin. Dehydropeptidase-1 (DPEP1) inhibitors have shown to avoid platin-induced nephrotoxicity without compromising its anticancer efficiency.

Exploring the Anticancer Potential of Phenolic -Triterpenes from Celastraceae Species.

To explore new compounds with antitumour activity, fifteen phenolic -tripterpenes isolated from Celastraceae species, , and , have been studied. Their chemical structures were elucidated through spectroscopic and spectrometric techniques, resulting in the identification of three novel chemical compounds. Evaluation on human tumour cell lines (A549 and SW1573, non-small cell lung; HBL-100 and T-47D, breast; HeLa, cervix, and WiDr, colon) revealed that three compounds, named 6-oxo-pristimerol, demethyl-zeylasteral, and zeylasteral, exhibited significant activity (GI ranging from 0.

Msc1 is a nuclear envelope protein that reinforces DNA repair in late mitosis.

Precise double-strand break (DSB) repair is a paramount for genome stability. Homologous recombination (HR) repairs DSBs when cyclin-dependent kinase (CDK) activity is high, which correlates with the availability of the sister chromatid as a template. However, anaphase and telophase are paradoxical scenarios since high CDK favors HR despite sister chromatids being no longer aligned.

The CRISPR/Cas9 system forms a condensate in the yeast nucleus.

CRISPR/Cas9 gene editing technology has revolutionized genetic engineering. However, the nuclear dynamics of Cas9 in eukaryotic cells, particularly in the model organism , remains poorly understood. Here, we constructed yeast strains expressing fluorescently tagged Cas9 variants, revealing their accumulation in the nucleus over time.