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  • Abrahamson and coworkers recently demonstrated a distinct

    2019-10-09

    Abrahamson and coworkers (2009) recently demonstrated a distinct role of the podocyte in preservation and production of mature GBM-components such as α3/4/5(IV)-chains. This group further verified that collagen receptors (integrins) are linked to the CC-4047 of podocytes. In accordance to this data, our study points to a similar function of DDR1 in maintenance of podocyte\'s cytoskeleton and architecture (Fig. 2). This function of DDR1 seems not to rely on integrin-signaling, as DDR1 is activated independently from integrins (Vogel et al., 2000).
    Experimental procedures
    Acknowledgements The authors want to thank the staff of the animal facilities at the Center of Molecular Medicine Cologne, at the MPI Experimental Medicine Goettingen and the Medical Faculty of the University of Goettingen for animal care. We thank Mrs. Andrea Bernhard and Mrs. Oya Goektas for excellent technical assistance. Parts of this CC-4047 work were presented as abstracts at the annual meetings of the German and the American Societies of Nephrology. This work was supported by grants from the Kidney Foundation of Canada (W.F.V.), the Cologne Fortune Program (O.G.) and is supported by the Deutsche Forschungsgemeinschaft DFGGR 1852/4-1 and 4-2 (O.G.).
    Introduction Insects dominate on earth, it is estimated that more than one million insects have been taxonomically identified. Previous investigations indicate that structurally novel and biological non-peptide small molecules (NPSMs) are present in insects [1], [2]. However, small molecules from insects and their roles in Nature, unlike plant or microorganism metabolites, are largely unknown. We became interested in insect metabolites and characterized a series of NPSMs from several insects [3], [4], [5], [6], [7]. Polyphaga plancyi Bolivar, a widely distributed insect species in China with blood stasis removing properties, has been used as a traditional Chinese medicine to treat a wide range of diseases such as amenorrhea and fracture. Modern pharmacological studies show that its extract possesses wide effects such as anticancer and anti-inflammatory properties [8]. In the course of our continuing study on insect NPSMs, the title insect were investigated, which led to the isolation of 8 NPSMs including five ones are new compounds (Fig. 1). Herein, we report their isolation, structure characterization and biological evaluation.
    Experimental
    Results and discussion Compound 1 has the molecular formula C10H11NO3 deduced from analysis of its positive HRESIMS ([M+Na]+, m/z 216.0630, calcd 216.0631), 13C NMR and DEPT spectra, indicating 6 degrees of unsaturation. The 1H NMR spectrum indicates the presence of four aromatic/olefinic protons at δH 7.50 (d, J=7.5Hz, H-6), 7.18 (t, J=7.3Hz, H-7), 7.22 (t, J=7.0Hz, H-8) and 6.93 (d, J=7.6Hz, H-9), indicating the presence of a 1,2-disubstituted benzene ring. The 13C NMR and DEPT spectra (Table 1) exhibit 10 carbon resonances ascribe to one methylene, six methine (four sp2 and two sp3 both oxygenated), and three quaternary carbons (a carbonyl). The structure construction of 1 was performed by 2D NMR experiments (Fig. 2). The 1H-1H COSY spectrum shows correlations of 3-OH (δH 4.86)/H-3/H-4/H-5/5-OH (δH 5.54). The HMBC correlations of NH (δH 9.78)/C-2, C-3, C-5a, C-9 and C-9a, H-3, H-4/C-2, H-5/C-6, C-5a and C-9a suggest the presence of a seven-membered lactam ring as shown. With exoskeleton in hand, the planar structure of 1 was readily determined. There are two chiral centers in 1, ROESY correlations of H-3/5-OH and H-5/3-OH evidently imply the relative configuration of 1. To clarify the absolute configuration of 1, computational methods were utilized. DFT and TD-DFT calculations were carried out at 298K in the gas phase with Gaussian 09 [10]. Conformational search were completed by using the Conflex 7 software, then optimized at the B3LYP/6-311G(d,p) level in the gas phase by using the Gaussian 09 software package. Based on the result of ECD calculations which were conducted at the B3LYP/6-31G//B3LYP/6-31G level in MeOH (Fig. 3), the absolute configuration of 1 was assigned as 3R,5R. Therefore, the structure of 1 was established and named as plancyamide A.