2130-96-3Relevant academic research and scientific papers
Discovery and development of substituted tyrosine derivatives as Bcl-2/Mcl-1 inhibitors
Liu, Renshuai,Liu, Lulu,Liu, Tingting,Yang, Xinying,Wan, Yichao,Fang, Hao
, p. 4907 - 4915 (2018)
Anti-apoptotic Bcl-2 family proteins are vital for cancer cells to escape apoptosis, which make them attractive targets for cancer therapy. Recently, a lead compound 1 was found to modestly inhibit the binding of BH3 peptide to Bcl-2 protein with a Ki value of 5.2 μM. Based on this, a series of substituted tyrosine derivatives were developed and tested for their binding affinities to Bcl-2 protein. Results indicated that these compounds exhibited potent binding affinities to Bcl-2 and Mcl-1 protein but not to Bcl-XL protein. Promisingly, compound 6i inhibited the binding of BH3 peptide to Bcl-2 and Mcl-1 protein with a Ki value of 450 and 190 nM respectively, and showed obvious anti-proliferative activities against tested cancer cells.
Mn(II) Complex of Lipophilic Group-Modified Ethylenediaminetetraacetic Acid (EDTA) as a New Hepatobiliary MRI Contrast Agent
Chen, Keyu,Cheng, Tao,Li, Pan,Shen, Chengyi,Wu, Changqiang,Xia, Qian,Xia, Zhiyang,Xiao, Bin,Zhang, Xiaoming,Zhong, Lei,Zhu, Chunrong,Zhu, Jiang
, p. 9182 - 9192 (2021/07/19)
Liver-specific contrast agents (CAs) can improve the Magnetic resonance imaging (MRI) detection of focal and diffuse liver lesions by increasing the lesion-to-liver contrast. A novel Mn(II) complex, Mn-BnO-TyrEDTA, with a lipophilic group-modified ethylenediaminetetraacetic acid (EDTA) structure as a ligand to regulate its behavior in vivo, is superior to Gd-EOB-DTPA in terms of a liver-specific MRI contrast agent. An MRI study on mice demonstrated that Mn-BnO-TyrEDTA can be rapidly taken up by hepatocytes with a combination of hepatobiliary and renal clearance pathways. Bromosulfophthalein (BSP) inhibition imaging, biodistribution, and cellular uptake studies confirmed that the mechanism of hepatic targeting of Mn-BnO-TyrEDTA is the hepatic uptake of the amphiphilic anion contrast agent mediated by organic anion transporting polypeptides (OATPs) expressed by functional hepatocytes.
Design, synthesis and preliminary bioactivity studies of indomethacin derivatives as Bcl-2/Mcl-1 dual inhibitors
Chen, Chen,Nie, Yiming,Xu, Guangsen,Yang, Xinying,Fang, Hao,Hou, Xuben
, p. 2771 - 2783 (2019/05/15)
Bcl-2 family proteins, which divides into pro-apoptosis proteins and anti-apoptosis proteins, are involved in cell apoptosis progression. As numerous studies illustrated, targeting Bcl-2 family proteins is more and more attractive and practicable to cancer treatment. In this work, we designed and synthesized a series of indomethacin derivatives as new inhibitors for Bcl-2 family proteins. Our results of binding assay to Bcl-2 proteins, MTT assay and apoptotic assay indicated that some compounds had potent binding affinity to Bcl-2/Mcl-1 but not Bcl-XL. Furthermore, compound 8j showed improved anti-proliferative activity than known Bcl-2 inhibitor WL-276.
Naamine derivatives, preparation method of Nammine derivatives, and application of Nammine derivatives in treatment of plant viruses and bacterial diseases
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Paragraph 0032-0034, (2018/05/16)
The invention discloses Naamine derivatives, a preparation method of the Nammine derivatives, and an application of the Nammine derivatives in treatment of plant viruses and bacterial diseases. The Nammine derivatives specifically are compounds represented as formulae from I-1 to I-16. During each reaction, materials participating in the reaction are taken according to the molar ratio required bythe reaction; excess substances are selected to participate in the reaction so as to ensure the reaction process of a target product; the pH value and reacting temperature and time of a system are determined according to the reaction type; and purifying separation or drying is carried out after the preparation. The Naamine derivatives provided by the invention exhibit good activity for treating plant viruses and bacterial diseases, and can well inhibit the following 14 species of plant pathogenic bacteria: tobacco mosaic virus (TMV), Fusarium oxysporum (Schl.)F.sp cucumerinum Owen, cercosporaarachidicola, Botryospuaeria berengeriana, Rhizotonia cerealis van der Hoeven apud.Boerema & Verhoeven, Helminthosporium maydis Nisik & Miy, Colleetotrichum lagenarium (Pass.) Ell. et Halst, fusariummoniliforme, Alternaria solani, FusaHum graminearum, Phytophthora infestans, phytophthora capsici, sclerotinia sclerotiorum, Botrytis cinerea and Thanatephorus cucumeris.
Total Synthesis of (?)-Spiroleucettadine
Lamb, Richard A.,Aberle, Nicholas S.,Lucas, Nigel T.,Lessene, Guillaume,Hawkins, Bill C.
, p. 14663 - 14666 (2017/10/25)
One of a number of intriguing new alkaloids isolated from the Leucetta sp. sponge in 2004, spiroleucettadine displayed unique structural features on a restricted scaffold: a trans-fused 5,5-bicyclic ring system together with an amino hemiketal moiety. Attempts to synthesize the initially proposed structure failed, raising questions as to its veracity, and structure revision ensued in 2008; no successful synthetic approach has been reported to date. Herein, we describe the enantiospecific total synthesis of (?)-spiroleucettadine by a highly efficient biomimetic approach starting from l-tyrosine. One of two key hypervalent-iodine-mediated oxidation reactions forged the spirocyclic center, and the other enabled the installation of the methylamine side chain in the penultimate step. Our approach provides synthetic access to a new class of spiroannulated natural products and will enable future studies of the structure–biological-activity relationships of these antibacterial compounds.
Improved binding affinities of pyrrolidine derivatives as Mcl-1 inhibitors by modifying amino acid side chains
Wan, Yichao,Liu, Tingting,Li, Xiaoxian,Chen, Chen,Fang, Hao
, p. 138 - 152 (2016/12/22)
As an important member of anti-apoptotic Bcl-2 protein, myeloid cell leukemia sequence 1 (Mcl-1) protein is an attractive target for cancer therapy. In this study, a new series of pyrrolidine derivatives as Mcl-1 inhibitors were developed by mainly modifying the amino acid side chain of compound 1. Among them, compound 18 (Ki= 0.077 μM) exhibited better potent inhibitory activities towards Mcl-1 protein compared to positive control Gossypol (Ki= 0.18 μM). In addition, compound 40 possessed good antiproliferative activities against PC-3 cells (Ki= 8.45 μM), which was the same as positive control Gossypol (Ki= 7.54 μM).
Design, synthesis, and in vitro and biological evaluation of potent amino acid-derived thiol inhibitors of the metallo-β-lactamase IMP-1
Arjomandi, Omid Khalili,Hussein, Waleed M.,Vella, Peter,Yusof, Yusralina,Sidjabat, Hanna E.,Schenk, Gerhard,McGeary, Ross P.
, p. 318 - 327 (2016/04/05)
There are currently no clinically available inhibitors of metallo-β-lactamases (MBLs). These enzymes confer resistance to bacteria against a broad range of commonly used β-lactam antibiotics, and are produced by an increasing number of bacterial pathogens. In this study, several thiol derivatives of l-amino acids were designed and synthesized, and their inhibitory effects against the metallo-β-lactamase IMP-1 (subclass B1) were investigated. The most potent compound, derived from l-tyrosine, exhibited competitive inhibition, with a Ki of 86 nM. The ability of this compound to render MBL-expressing bacteria susceptible to imipenem was examined. Reductions in MIC values up to 5.2 - fold were observed.
Structure and absolute configuration of auriculamide, a natural product from the predatory bacterium herpetosiphon aurantiacus
Schieferdecker, Sebastian,Domin, Nicole,Hoffmeier, Christine,Bryant, Donald A.,Roth, Martin,Nett, Markus
, p. 3057 - 3062 (2015/05/13)
The genome of the filamentous, predatory bacterium Herpetosiphon aurantiacus harbors a plethora of genes that are predicted to be involved in natural product biosynthesis. Until now, however, no secondary metabolites have been described from this microorganism. Analysis of H. aurantiacus culture extracts by 1H NMR spectroscopy now led to the discovery of a chlorinated amide, which we termed auriculamide. The configuration of the three chiral centers in auriculamide was solved by chromatographic comparison with stereospecifically prepared reference compounds following chemical degradation. Furthermore, a putative gene cluster for the biosynthesis of auriculamide was identified by genome mining. Chemical analysis of culture extracts from the predatory bacterium Herpetosiphon aurantiacus led to the discovery of the new natural product auriculamide, the structure of which was elucidated by MS and NMR analyses. The absolute configuration was determined, after hydrolysis, by chromatographic comparison with synthetic standards. A gene cluster for the biosynthesis of auriculamide is proposed.
Preparation and biological evaluation of key fragments and open analogs of scleritodermin A
Sellanes, Diver,Campot, Francisco,Nú?ez, Ivana,Lin, Gerardo,Espósito, Pablo,Dematteis, Sylvia,Salda?a, Jenny,Domílnguez, Laura,Manta, Eduardo,Serra, Gloria
experimental part, p. 5384 - 5395 (2010/08/19)
The synthesis of key fragments of scleritodermin A, their assembly, and their biological evaluation as cytotoxic and anthelmintic were performed.Highlights of the synthetic route include formation of the a-ketoamide linkage and use of stereocontrolled reactions.Open analogs of this natural product were obtained using a convergent strategy.
PROTEIN TYROSINE PHOSPHATASE 1B INHIBITOR, PREPARATION METHODS AND USES THEREOF
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Page/Page column 32, (2009/12/27)
PTP1B inhibitors with the following structure (formula I). Experiments indicate that these inhibitors can effectively inhibit the activity of protein tyrosine phosphatase 1B (PTP1B). They can be used as insulin sensitisers. They can be used to prevent, delay or treat diseases which are related to insulin antagonism mediated by PTP1B, especially diabetes type II and obesity. The invention also provides methods for preparing these inhibitors.
