Impact delivery of prebiotic compounds to the early Earth from an impacting comet is considered to be one of the possible ways by which prebiotic molecules arrived on the Earth. Given the ubiquity of impact features observed on all planetary bodies, bolide impacts may be a common source of organics on other planetary bodies both in our own and other solar systems. Biomolecules such as amino acids have been detected on comets and are known to be synthesized due to impact-induced shock processing. Here we report the results of a set of hypervelocity impact experiments where we shocked icy mixtures of amino acids mimicking the icy surface of planetary bodies with high-speed projectiles using a two-stage light gas gun and analyzed the ejecta material after impact. Electron microscopic observations of the ejecta have shown the presence of macroscale structures with long polypeptide chains revealed from LCMS analysis. These results suggest a pathway in which impact on cometary ices containing building blocks of life can lead to the synthesis of material architectures that could have played a role in the emergence of life on the Earth and which may be applied to other planetary bodies as well.
Despite extensive studies and the great variety of existing anticancer agents, cancer treatment remains an aggravating and challenging problem. Therefore, the development of novel anticancer drugs with a better therapeutic profile and fewer side effects to combat this persistent disease is still necessary. In this study, we report a novel series of benzothiazole and chromone derivatives that were synthesized and evaluated for their anticancer activity as an inhibitor of ATR kinase, a master regulator of the DDR pathway. The cell viability of a set of 25 compounds was performed using MTT assay in HCT116 and HeLa cell lines, involving 72 h incubation of the compounds at a final concentration of 10 µM. Cells incubated with compounds 2c, 7h and 7l were found to show viability ≤50%, and were taken forward for dose–response studies. Among the tested compounds, three of them (2c, 7h and 7l) showed higher potency, with compound 7l exhibiting the best IC50 values in both the cell lines. Compounds 2c and 7l were found to be equally cytotoxic towards both the cell lines, namely, HCT116 and HeLa, while compound 7h showed better cytotoxicity towards HeLa cell line. For these three compounds, an immunoblot assay was carried out in order to analyze the inhibition of phosphorylation of Chk1 at Ser 317 in HeLa and HCT116 cells. Compound 7h showed inhibition of pChk1 at Ser 317 in HeLa cells at a concentration of 3.995 µM. Further analysis for Chk1 and pChk1 expression was carried out in Hela cells by treatment against all the three compounds at a range of concentrations of 2, 5 and 10 µM, wherein compound 7h showed Chk1 inhibition at 2 and 5 µM, while pChk1 expression was observed for compound 7l at a concentration of 5 µM. To support the results, the binding interactions of the compounds with the ATR kinase domain was studied through molecular docking, wherein compounds 2c, 7h and 7l showed binding interactions similar to those of Torin2, a known mTOR/ATR inhibitor. Further studies on this set of molecules is in progress for their specificity towards the ATR pathway.
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