13278-36-9Relevant academic research and scientific papers
Use of pyridine as cocatalyst for the synthesis of N-phenylanthranilic acids
Pellon, Rolando F.,Mamposo, Taimirys,Carrasco, Ramon,Rodes, Lorenzo
, p. 3877 - 3883 (1996)
The use of pyridine is reported as cocatalyst for the synthesis of N-phenylanthranilic acids by the Ullmann-Goldberg condensation in water or amyl alcohol as solvents, with good yield.
Structure-Polymorphism Study of Fenamates: Toward Developing an Understanding of the Polymorphophore
López-Mejías, Vilmalí,Matzger, Adam J.
, p. 3955 - 3962 (2015)
The ability of molecules to adopt more than one unique crystalline structure, polymorphism, is a phenomenon of considerable scientific interest because it challenges the notion that molecules arrange themselves exclusively in the thermodynamically most stable crystal form. The factors influencing this behavior are manifold and have defied simple prediction. To illustrate an approach to elucidating these factors, the solid-state behavior of a series of molecules that are derivatives of tolfenamic acid (TA), a pentamorphic system, was explored. In analogy to the manner in which drugs are discovered through structure-activity relationships and the identification of a pharmacophore, we test here the notion that when a collective ensemble structural motifs, a "polymorphophore," is incorporated into a molecule it renders the compound polymorphic. The structure-polymorphism relationship in six TA analogues, both commercial and newly synthesized, was undertaken with the intention of systematically understanding the factors that influence the polymorphism in the fenamic acid class through a combined computational as well as experimental approach. Ultimately, such studies may be used to experimentally derive the propensity for polymorphic behavior of a given molecular motif and perhaps provide a pathway to engineer molecular compounds with controlled properties in the solid state.
Design, synthesis and bioactivity evaluation of novel evodiamine derivatives with excellent potency against gastric cancer
Liang, Ziyi,Lei, Fang,Deng, Jiedan,Zhang, Honghua,Wang, Yuqing,Li, Junfang,Shi, Tao,Yang, Xiaoyan,Wang, Zhen
, (2021/11/22)
Gastric cancer represents a significant health burden worldwide. Previously, inspired by the traditional Chinese medicine Wu-Chu-Yu to treat the spleen and stomach system for thousands of years, we identified N14-phenyl substituted evodiamine derivatives as potential antitumor agents with favorable inhibition on Top1. Herein, structural optimization and structure-activity relationship studies (SARs) led us to discovering a highly active evodiamine derivative compound 6t against gastric cancer. Further anti-tumor mechanism studies revealed that compound 6t played as the inhibition of topoisomerase 1 (Top1), effectively induced apoptosis, obviously arrested the cell cycle at the G2/M phase, and significantly inhibited the migration and invasion of SGC-7901 and MGC-803 cell lines in a dose-dependent manner. Moreover, the compound 6t was low toxicity in vivo and exhibited excellent anti-tumor activity (TGI = 70.12%) in the MGC-803 xenograft models. In summary, compound 6t represents a promising candidate as a potential chemotherapeutic agent against gastric cancer.
Design, synthesis and bioactivity evaluation of novel N-phenyl-substituted evodiamine derivatives as potent anti-tumor agents
Hao, Xiangyong,Deng, Jiedan,Zhang, Honghua,Liang, Ziyi,Lei, Fang,Wang, Yuqing,Yang, Xiaoyan,Wang, Zhen
, (2022/01/10)
Natural products are important sources for the development of therapeutic medicine, among which evodia fruit has a wide range of medicinal properties in traditional Chinese medicine. Evodiamine, the main active component of evodia fruit, has various anti-cancer effects and has been proved to be a Topo inhibitor. From our previous attempts of modifying evodiamine, we found that the N14 phenyl substituted derivatives had showed great anti-tumor activity, which prompted us to further explore the novel structures and activities of these compounds. Compound 6f, as a N14 3-fluorinated phenyl substituted evodiamine derivative, showed a certain inhibitory activity against Topo I at 200 μM. By studying its anti-tumor effects in vitro, compound 6f could inhibit proliferation and induce apoptosis, as well as arrest the cell cycle of HGC-27 and HT-29 cell lines at G2/M phase in a concentration-dependent manner. Moreover, compound 6f could inhibit the migration and invasion of HGC-27 cell lines. Meanwhile, compound 6f could induce apoptosis of HGC-27 cells by inhibiting PI3K/AKT pathway. Overall, this work demonstrated that the N14 phenyl-substituted evodiamine derivatives had a good inhibitory effect on tumor cells in vitro, providing a promising strategy for developing potential anticancer agents for the treatment of gastrointestinal tumors.
Design, synthesis and biological evaluation of N-anthraniloyl tryptamine derivatives as pleiotropic molecules for the therapy of malignant glioma
Fan, Xiaohong,Li, Junfang,Long, Lin,Shi, Tao,Liu, Dan,Tan, Wen,Zhang, Honghua,Wu, Xiaoyan,Lei, Xiaoyong,Wang, Zhen
, (2021/06/09)
COX-2 and STAT3 are two key culprits in the glioma microenvironment. Herein, to inhibit COX-2 and block STAT3 signaling, we disclosed 27 N-anthraniloyl tryptamine compounds based on the combination of melatonin derivatives and N-substituted anthranilic acid derivatives. Among them, NP16 showed the best antiproliferative activity and moderate COX-2 inhibition. Of note, NP16 decreased the level of p-JAK2 and p-STAT3, and blocked the nuclear translocation of STAT3 in GBM cell lines. Moreover, NP16 downregulated the MMP-9 expression of BV2 cells in a co-culture system of BV2 and C6 glioma cells, abrogated the proliferative/invasive/migratory abilities of GBM cells, induced apoptosis by ROS and the Bcl-2-regulated apoptotic pathway, and induced obvious G2/M arrest in glioma cells in vitro. Furthermore, NP16 displayed favorable pharmacokinetic profiles covering long half-life (11.43 ± 0.43 h) and high blood-brain barrier permeability. Finally, NP16 effectively inhibited tumor growth, promoted the survival rate, increased the expression of E-cadherin and reduced overproduction of PGE2, MMP-9, VEGF-A and the level of p-STAT3 in tumor tissue, and improved the anxiety-like behavior in C6 glioma model. All these evidences demonstrated N-anthraniloyl tryptamine derivatives as multifunctional anti-glioma agents with high potency could drain the swamp to beat glioma.
Development of potent and selective inhibitors of aldo-keto reductase 1C3 (type 5 17β-hydroxysteroid dehydrogenase) based on N -phenyl-aminobenzoates and their structure-activity relationships
Adeniji, Adegoke O.,Twenter, Barry M.,Byrns, Michael C.,Jin, Yi,Chen, Mo,Winkler, Jeffrey D.,Penning, Trevor M.
supporting information; experimental part, p. 2311 - 2323 (2012/05/04)
Aldo-keto reductase 1C3 (AKR1C3; type 5 17β-hydroxysteroid dehydrogenase) is overexpressed in castration resistant prostate cancer (CRPC) and is implicated in the intratumoral biosynthesis of testosterone and 5α-dihydrotestosterone. Selective AKR1C3 inhibitors are required because compounds should not inhibit the highly related AKR1C1 and AKR1C2 isoforms which are involved in the inactivation of 5α-dihydrotestosterone. NSAIDs, N-phenylanthranilates in particular, are potent but nonselective AKR1C3 inhibitors. Using flufenamic acid, 2-{[3-(trifluoromethyl)phenyl]amino}benzoic acid, as lead compound, five classes of structural analogues were synthesized and evaluated for AKR1C3 inhibitory potency and selectivity. Structure-activity relationship (SAR) studies revealed that a meta-carboxylic acid group relative to the amine conferred pronounced AKR1C3 selectivity without loss of potency, while electron withdrawing groups on the phenylamino B-ring were optimal for AKR1C3 inhibition. Lead compounds did not inhibit COX-1 or COX-2 but blocked the AKR1C3 mediated production of testosterone in LNCaP-AKR1C3 cells. These compounds offer promising leads toward new therapeutics for CRPC.
Synthesis of novel heme-interacting acridone derivatives to prevent free heme-mediated protein oxidation and degradation
Pal, Chinmay,Kundu, Milan Kumar,Bandyopadhyay, Uday,Adhikari, Susanta
supporting information; scheme or table, p. 3563 - 3567 (2011/08/06)
Heme is an important prosthetic molecule for various hemoproteins and serves important function in living aerobic organisms. But degradation of hemoprotein, for example, hemoglobin during different pathological conditions leads to the release of heme, which is very toxic as it induces oxidative stress and inflammation due to its pro-oxidant nature. Thus, synthesis of compound that will detoxify free heme by interacting with it would be fruitful for the management of heme-induced pathogenesis. Here, we report the synthesis of a novel natural product arborinine and some other acridone derivatives, which interact with free heme. These acridones in vitro block heme-mediated protein oxidation and degradation, markers for heme-induced oxidative stress.
Regioselective copper-catalyzed amination of bromobenzoic acids using aliphatic and aromatic amines
Wolf, Christian,Liu, Shuanglong,Mei, Xuefeng,August, Adam T.,Casimir, Michael D.
, p. 3270 - 3273 (2007/10/03)
A chemo- and regioselective copper-catalyzed cross-coupling procedure for amination of 2-bromobenzoic acids is described. The method eliminates the need for acid protection and produces N-aryl and N-alkyl anthranilic acid derivatives in up to 99% yield. N-(1-Pyrene)anthranilic acid has been employed in metal ion-selective fluorosensing. Titration experiments showed that this pyrene-derived amino acid forms an equimolar complex with Hg(II) in water resulting in selective fluorescence quenching even in the presence of other metal ions such as Zn(II) and Cd(II).
Regioselective copper-catalyzed amination of chlorobenzoic acids: Synthesis and solid-state structures of N-aryl anthranilic acid derivatives
Mei, Xuefeng,August, Adam T.,Wolf, Christian
, p. 142 - 149 (2007/10/03)
A chemo- and regioselective copper-catalyzed cross-coupling reaction for effective amination of 2-chlorobenzoic acids with aniline derivatives has been developed. The method eliminates the need for acid protection and produces a wide range of N-aryl anthranilic acid derivatives in up to 99% yield. The amination was found to proceed with both electron-rich and electron-deficient aryl chlorides and anilines and also utilizes sterically hindered anilines such as 2,6-dimethylaniline and 2-tert-butylaniline. The conformational isomerism of appropriately substituted N-aryl anthranilic acids has been investigated in the solid state. Crystallographic analysis of seven anthranilic acid derivatives showed formation of two distinct supramolecular architectures exhibiting trans-anti and unprecedented trans-syn dimeric structures.
Synthesis, biological evaluation, and molecular modeling of novel thioacridone derivatives related to the anticancer alkaloid acronycine
Dheyongera, James P.,Geldenhuys, Werner J.,Dekker, Theodor G.,Van Der Schyf, Cornelis J.
, p. 689 - 698 (2007/10/03)
The well-reported, but moderate antitumor activity of the acronycine alkaloid led us to synthesize a novel series of thioacridone compounds related to acronycine, as potential anticancer agents. Compounds were designed either as DNA intercalating agents, or as DNA intercalating agents with covalent bond forming potential. Bathochromic shifts of the compounds upon complexation with salmon testis DNA suggested intercalation as the mode of DNA binding. The binding interaction of the compounds was found to be approximately 10 2 M-1, with that of the most potent compound 1-(2-dimethylaminoethylamino)-9(10H)-thioacridone, 104 M -1. In vitro cytotoxic activity (IC50) against HL-60 cells was found to range between 3.5 and 22 μg/mL. QSAR analyses yielded a multiple linear regression equation with an r2 of 0.847 for DNA binding and an r2 of 0.575 for cytotoxicity. The physicochemical parameters used in the QSAR analyses were log P, polar surface area, and calculated molar refractivity. Docking studies were also performed to compare the binding of the most potent and least potent compounds in the study in order to predict desirable chemical characteristics for further exploitation in drug design efforts. The thioacridone compounds in this series demonstrate cytotoxic activity in vitro that merit future in vivo evaluation.
