6766-44-5Relevant articles and documents
Homocam ptothecin 5-ene norcantharidin acid ester derivative, and regioselective synthesis method thereof
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Paragraph 0025-0029, (2019/11/21)
The invention discloses a homocam ptothecin 5-ene norcantharidin acid ester derivative represented by fomula I, and a regioselective synthesis method thereof, wherein R is selected from C1-C6 alkyl, substituted alkyl, and cycloalkyl. It is confirmed by activity test that the homocam ptothecin 5-ene norcantharidin acid ester derivative I possesses excellent anti-tumor effect, and is especially highin inhibition activity on liver cancer, stomach cancer, colorectal carcinoma and pancreas cancer. According to the preparation method of the homocam ptothecin 5-ene norcantharidin acid ester derivative, the raw materials are easily available; cost is low; synthesis reaction regioselectivity is extremely high; target product yield is high; and preparation is convenient.
Synthesis and structure-activity relationship study of novel 3-heteroarylcoumarins based on pyridazine scaffold as selective MAO-B inhibitors
Costas-Lago, María Carmen,Besada, Pedro,Rodríguez-Enríquez, Fernanda,Vi?a, Dolores,Vilar, Santiago,Uriarte, Eugenio,Borges, Fernanda,Terán, Carmen
supporting information, p. 1 - 11 (2017/08/10)
Compounds of hybrid structure pyridazine-coumarin were discovered as potent, selective and reversible inhibitors of monoamine oxidase B (MAO-B). These compounds were synthesized in good yield following a multistep approach based on Knoevenagel reaction and using as key intermediate pyridazinone 16, which was obtained from maleic anhydride and furan. Compounds 9b and 9d are the most active compounds of these series, with IC50 values in the sub-micromolar range, and lack of cytotoxic effects. Theoretical calculation of ADME properties also suggested a good pharmacokinetic profile for both compounds. Docking simulations provided insights into enzyme inhibitor interactions and allowed us to rationalize the observed structure-activity relationships (SARs).
Albumin-polymer conjugate nanoparticles and their interactions with prostate cancer cells in 2D and 3D culture: Comparison between PMMA and PCL
Jiang, Yanyan,Lu, Hongxu,Dag, Aydan,Hart-Smith, Gene,Stenzel, Martina H.
, p. 2017 - 2027 (2016/03/22)
Using proteins as the hydrophilic moiety can dramatically improve the biodegradability and biocompatibility of self-assembled amphiphilic nanoparticles in the field of nanomedicine. In this study, we fabricated and evaluated curcumin loaded albumin-polycaprolactone nanoparticles as a novel drug delivery system for prostate carcinoma therapeutics and compared their performance to poly(methyl methacrylate) (PMMA), a non-degradable and amorphous polymer. The maleimide functionalized poly(ε-caprolactone) (PCL) was obtain using ring opening polymerization (ROP) of ε-caprolactone where N-(2-hydroxyethyl)maleimide was used as an initiator. The resorbable albumin-polymer conjugate was prepared by conjugating the hydrophobic maleimide-terminated PCL to the hydrophilic bovine serum albumin (BSA) via a simple Michael addition reaction. PMMA was conjugated in a similar manner. The amphiphilic BSA-polymer conjugates can self-assemble into nanoparticles, displaying well-defined structure, prolonged storage stability, and excellent biocompatibility. The BSA nanoparticles, with encapsulated curcumin, exhibited highly enhanced antitumor activity compared to free curcumin. Furthermore, the high efficacy of the curcumin loaded nanoparticles was verified by effectively inhibiting the growth of three-dimensional LNCaP multicellular tumour spheroids. The cytotoxicity was attributed to the efficient cellular uptake of the nanoparticles through caveolic endocytosis. The direct comparison between PCL and the PMMA revealed that drug loading and release as well as cytotoxicity is not significantly affected by the nature of the polymer. However, it seems that nanoparticles based on PMMA penetrate quicker into LNCaP multicellular tumour spheroids thanks to the increased stability. The faster penetration was found to reduce the toxicity of the nanoparticles as evidenced by the lower number of dead cells. In contrast, the fully degradable PCL-based nanoparticles were more efficient in delivering the drug, thus limiting the growth of LNCaP multicellular tumour spheroids.
