Concise Enantioselective Total Synthesis of Isopavine Alkaloids

Herein, we report a concise asymmetric total synthesis of isopavine alkaloids, which feature a special azabicyclo[3.2.2]­nonane tetracyclic skeleton. The key steps include iridium-catalyzed asymmetric hydrogenation of unsaturated carboxylic acids, Curtius rearrangement, and Eschweiler–Clarke methylation, which enable an enantioselective approach to isopavine alkaloids in 6–7 linear steps. Furthermore, for the first time, isopavine alkaloids, especially (−)-reframidine (3), are found to display effective antiproliferative effects on various cancer cell lines

Efficient synthesis of novel colchicine-magnolol hybrids and evaluation of their inhibitory activity on key proteases of 2019-nCoV replication and acute lung injury

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or 2019-nCoV), is a life-threatening infectious condition. Acute lung injury is a common complication in patients with COVID-19. 3-chymotrypsin-like protease (3CLpro) of 2019-nCoV and neutrophil elastase are critical targets of COVID-19 and acute lung injury, respectively. Colchicine and magnolol are reported to exert inhibitory effects on inflammatory response, the severe comorbidity in both COVID-19 and acute lung injury. We thus designed and synthesized a series of novel colchicine-magnolol hybrids based on a two-step synthetic sequence. It was found that these novel hybrids provided unexpected inhibition on 3CLpro and neutrophil elastase, a bioactivity that colchicine and magnolol did not possess. These findings not only provide perquisites for further in vitro and in vivo investigation to confirm the therapeutic potentiality of novel colchicine-magnolol hybrids, but also suggest that the concurrent inhibition of 3CLpro and neutrophil elastase may enable novel colchicine-magnolol hybrids as effective multi-target drug compounds.</p

Comparative study of volatile components from male and female flower buds of <i>Populus</i> × <i>tomentosa</i> by HS-SPME-GC-MS

<p>The differences of volatile components in male (MFB) and female flower buds (FFB) of <i>Populus</i> × <i>tomentosa</i> were analysed and compared by HS-SPME with GC-MS for the first time. A total of 34 compounds were identified. Two clusters were clearly divided into male and female by hierarchical clustering analysis. Both the male and female flower buds showed methyl salicylate (22.83 and 24.09%, respectively) and 2-hydroxy-benzaldehyde (10.05 and 12.41%, respectively) as the main volatile constituents. The content of 2-cyclohexen-1-one, benzyl benzoate, and methyl benzoate in FFB was remarkably higher than in MFB. In contrast, the content of ethyl benzoate in MFB was greater than that in FFB. The phenomena showed the characteristic differences between MFB and FFB of <i>P.</i> × <i>tomentosa</i>, which enriched the basic studies on dioecious plant.</p

FTIR spectra of the titration of the CK, NPK, NPKM and M treatment depending on the concentrations of CaCl₂changes(from 0mmol/L to 100mmol/L).

<p>FTIR spectra of the titration of the CK, NPK, NPKM and M treatment depending on the concentrations of CaCl₂changes(from 0mmol/L to 100mmol/L).</p

Fluorescence excitation-emission matrix (EEM) spectra of dissolved organic matter (DOM) for soils from the CK, NPK, NPKM and M treatments, respectively, in the long term experiment.

<p>Specifically, Peaks A(Ex/Em of 240/420), B(Ex/Em of 320/420), C(Ex/Em of 280/350) and D(Ex/Em of 230/420)referred to fulvic acid-like (peaks A and D), humic acid-like (peak B) and protein-like (peak C) substances, respectively.</p

Synchronous and asynchronous 2D correlation maps generated from the 1800–900 cm^-1 region of the FTIR spectra of dissolved organic matter in the CK, NPK, and NPKM treatments over Ca²⁺.

<p>Red represents positive correlation, and blue represents negative correlation; a higher color intensity indicates a stronger positive or negative correlation.</p

High resolution transmission electron microscopy (HRTEM) images of soil dissolved organic matter from CK(a), NPK(b), NPKM(c) and M(d).

<p>A:TEM images; B:HRTEM images and selected area electron diffraction pattern of the three regions (black region is completely crystalline, whereas the gray region remains amorphous); C:EDS images.</p

DataSheet1_Design, synthesis and biological evaluation of a novel colchicine-magnolol hybrid for inhibiting the growth of Lewis lung carcinoma in Vitro and in Vivo.docx

Colchicine is a bioactive alkaloid originally from Colchicum autumnale and possesses excellent antiproliferative activity. However, colchicine-associated severe toxicity, gastrointestinal side effects in particular, limits its further therapeutic use. In the current study, we thus designed and synthesized a novel hybrid (CMH) by splicing colchicine and magnolol, a multifunctional polyphenol showing favorable gastrointestinal protection. The antitumor activity of CMH in Lewis lung carcinoma (LLC) was then evaluated in vitro and in vivo. Biologically, CMH inhibited the growth of LLC cells with an IC50 of 0.26 μM, 100 times more potently than cisplatin (26.05 μM) did. Meanwhile, the cytotoxicity of CMH was 10-fold lower than that of colchicine in normal human lung cells (BEAS-2B). In C57BL/6 mice xenograft model, CMH (0.5 mg/kg) worked as efficacious as colchicine (0.5 mg/kg) to inhibit tumor growth and 2 times more potently than cisplatin (1 mg/kg). In terms of mortality, 7 out of 10 mice died in colchicine group (0.75 mg/kg), while no death was observed in groups receiving CMH or cisplatin at 0.75 mg/kg. Mechanistic studies using Western blot revealed that CMH dose-dependently suppressed the protein expression of phosphorylated ERK. Molecular docking analysis further indicated that CMH was well fitted in the colchicine binding site of tubulin and formed several hydrogen bonds with tubulin protein. These results enable our novel hybrid CMH as a potential antineoplastic agent with lower toxicity, and provide perquisites for further investigation to confirm the therapeutic potentiality of this novel hybrid.</p