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211.
The problem of the scattering of a plane, monochromatic, linearly polarized, electromagnetic wave incident from vacuo onto a linear, homogeneous, non-magnetic, spatially dispersive sphere whose dielectric function is of the form is solved within the framework of Maxwell's theory. 相似文献
212.
Abstract Taking advantage of the'heavy atom'effect, we have recently prepared a series of nine novel halogenated and sulfur-substituted benzophenoxazines which have enhanced intersystem crossing to the triplet state as measured by singlet oxygen photobleaching of 1,3-diphenylisobenzofuran. The dyes were evaluated for their dark and light-induced toxicities towards several carcinomata and normal primary cell lines. One of these days, 5-amino-6-iodo-9-diethylaminobenzol[a]phenoxazinium chloride, was found to be a potent photosensitizer for a murine sarcoma 180 and four human carcinomata cell lines (larynx Hep2, cervical HeLa, rectal tumor cell HRT, and transitional-cell bladder BTC). Several dyes caused marked light dependent killing of two tumor cell lines (Hep2 and HRT) but were minimally toxic to a normal bovine fetal kidney (BFK) line. Sulfur substitutuion into the benzophenoxazine nucleus results, under the conditions studied, in the largest enhancement of phototoxicity both to normal and cancer cells. Comparisons between appropriate dyes show a correlation between the efficiency of singlet oxygen generation and phototoxicity. These results suggest that the photosensitizing efficacy of certain cationic benzophenoxazinium chromophores, such as Nile Blue A, can be greatly increased by appropriate structural modification. The demonstrated selectivity for carcinoma cells by some of these new photosensitizers may be useful therapeutically. 相似文献
213.
Fragment-based drug discovery is an important and increasingly reliable technology for the delivery of clinical candidates. Notably, however, sp3-rich fragments are a largely untapped resource in molecular discovery, in part due to the lack of general and suitably robust chemical methods available to aid their development into higher affinity lead and drug compounds. This Perspective describes the challenges associated with developing sp3-rich fragments, and succinctly highlights recent advances in C(sp3)–H functionalisations of high potential value towards advancing fragment hits by ‘growing’ functionalised rings and chains from unconventional, carbon-centred vectors.This Perspective reviews recently developed methods that are likely to be of value to the elaboration of sp3-rich fragments from carbon-centred vectors, whilst maintaining key fragment-to-target binding interactions. 相似文献
214.
Assist. Prof. Luca Laraia Dr. Guillaume Garivet Dr. Daniel J. Foley Dr. Nadine Kaiser Dr. Sebastian Müller M. Sc. Sarah Zinken Thomas Pinkert M. Sc. Julian Wilke Dr. Dale Corkery Dr. Axel Pahl Dr. Sonja Sievers Dr. Petra Janning Prof. Dr. Christoph Arenz Prof. Yaowen Wu Prof. Raphaël Rodriguez Prof. Dr. Herbert Waldmann 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(14):5770-5778
Chemical proteomics is widely applied in small-molecule target identification. However, in general it does not identify non-protein small-molecule targets, and thus, alternative methods for target identification are in high demand. We report the discovery of the autophagy inhibitor autoquin and the identification of its molecular mode of action using image-based morphological profiling in the cell painting assay. A compound-induced fingerprint representing changes in 579 cellular parameters revealed that autoquin accumulates in lysosomes and inhibits their fusion with autophagosomes. In addition, autoquin sequesters Fe2+ in lysosomes, resulting in an increase of lysosomal reactive oxygen species and ultimately cell death. Such a mechanism of action would have been challenging to unravel by current methods. This work demonstrates the potential of the cell painting assay to deconvolute modes of action of small molecules, warranting wider application in chemical biology. 相似文献