Structure–activity relationships and the cytotoxic effects of novel diterpenoid alkaloid derivatives against A549 human lung carcinoma cells

The cytotoxicity of three alkaloids from the roots of Aconitum yesoense var. macroyesoense as well as 36 semi-synthetic C20-diterpenoid atisine-type alkaloid derivatives against A549 human lung carcinoma cells was examined. Ten acylated alkaloid derivatives, pseudokobusine 11-veratroate (9), 11-anisoate (12), 6,11-dianisoate (14), 11-p-nitrobenzoate (18), 11,15-di-p-nitrobenzoate (22), 11-cinnamate (25) and 11-m-trifluoromethylbenzoate (27), and kobusine 11-p-trifluoromethylbenzoate (35), 11-m-trifluoromethylbenzoate (36) and 11,15-di-p-nitrobenzoate (39), exhibited cytotoxic activity, and 11,15-dianisoylpseudokobusine (16) was found to be the most potent cytotoxic agent. Their IC50 values against A549 cells ranged from 1.72 to 5.44 μM. In the occurrence of cytotoxic effects of atisine-type alkaloids, replacement by an acyl group at both C-11 and C-15 resulted in the enhancement of activity of the parent alkaloids compared to that from having hydroxy groups at this position, and the presence of a hydroxy group at the C-6 position was required for the cytotoxic effects. These acylated alkaloid derivatives inhibit cell growth through G1 arrest

Label-free tomographic imaging of nanodiamonds in living cells

Nanodiamonds have acknowledged growing attention due to their facile functionalization, stable fluorescence, low toxicity, and decent biocompatibility. However, despite advances applications of nanodiamonds in drug delivery, catalysis and bio-sensing, laser irradiation still limits long-time tracking of nanodiamonds in living cells due to phototoxicity. Here, using optical diffraction tomography, we performed quantitative morphological and biophysical analysis of living cells via endocytosis or electroporation of nanodiamonds (5 nm, 35 nm, and 100 nm) without the need for a fluorescence label. Optical diffraction tomography is an inexpensive and noninvasive microscopy technique, which images cells and subcellular structures as a function of their refractive index. The laser excitation power is much weaker than in the case of fluorescence microscopy, which reduces phototoxicity. Thanks to the very high refractive index of diamond, nanodiamonds in HeLa cells can be clearly discriminated from cellular structures using optical diffraction tomography. As an application, we show that aggregation and deaggregation of internalized nanodiamonds can be detected via changes in the refractive index distribution of the entire cell. Optical diffraction tomography successively images prevention of in-cell particle aggregation through polyglycerol coating of nanodiamonds. In the case of endocytosis, optical diffraction tomography shows deaggregation of nanodiamonds after a prolonged incubation time. Together, our findings implicate that refractive index measurements are a favorable tool to track nano-diamonds, without a fluorescent label, inside living cells. This could be useful to study real-time therapeutic or metabolic activities in living cells using very weak laser irradiation. Finally, the elaborate creation of fluorescent defects in nanodiamonds becomes redundant.ISSN:0925-9635ISSN:1879-006

Cell of origin and mutation pattern define three clinically distinct classes of sebaceous carcinoma

Sebaceous carcinomas (SeC) are cutaneous malignancies that sometimes metastasize and cause death. Here the authors perform whole-exome sequencing on 32 SeC and report distinct mutational classes that may explain cancer ontogeny and clinical outcome