Discovery of N-substituted 3-arylisoquinolone derivatives as antitumor agents originating from O-substituted 3-arylisoquinolines via [2,3] or [3,3] rearrangement

Li, Bo; Wang, Gaihong; Xu, Zhijian; Zhang, Yong; Huang, Xiangui; Zeng, Bu‐Bing; Chen, Kaixian; Shi, Jiye; Wang, He-Yao; Zhu, Weiliang

doi:10.1016/j.ejmech.2014.03.008

Cited by 11 publications

(4 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The novel benzoazepinoisoquinolone 23 , a seven membered B-ring of oxyberberine, was reported with anti-tumor activity against cell lines originating from human tumors. The IC 50 value of compound 23 was 2.80 μmol/L for HCT116 cells ( Figure 8 ) 100 , 101 .…”

Section: Structure-activity Relationships Of the Derivatives Of Berbementioning

confidence: 98%

Advances in the study of berberine and its derivatives: a focus on anti-inflammatory and anti-tumor effects in the digestive system

et al. 2016

Self Cite

View full text Add to dashboard Cite

It has been widely recognized that inflammation, particularly chronic inflammation, can increase the risk of cancer and that the simultaneous treatment of inflammation and cancer may produce excellent therapeutic effects. Berberine, an alkaloid isolated from Rhizoma coptidis, has broad applications, particularly as an antibacterial agent in the clinic with a long history. Over the past decade, many reports have demonstrated that this natural product and its derivatives have high activity against both cancer and inflammation. In this review, we summarize the advances in studing berberine and its derivatives as anti-inflammatory and anti-tumor agents in the digestive system; we also discuss their structure-activity relationship. These data should be useful for the development of this natural product as novel anticancer drugs with anti-inflammation activity.

show abstract

Section: Structure-activity Relationships Of the Derivatives Of Berbementioning

confidence: 98%

Advances in the study of berberine and its derivatives: a focus on anti-inflammatory and anti-tumor effects in the digestive system

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, the substitution of the hydrogen at the 2-position resulted in the loss of selectivity (3 a' (Figure 1). [10] According to this result 13 analogues of 3 a were synthesized and 3 h was obtained with the obviously improved hCES2A inhibitory effects and excellent selectivity ( Figure 2)…”

Section: Introductionmentioning

confidence: 94%

“…3 a, 3 a' and 3 e have reported in our previous work. [9][10] 3-(4-(benzyloxy)-3-methoxyphenyl)-7,8-dimethoxy-isoquinolin-1(2H) 8-(3-methoxy-4-(methoxymethoxy)phenyl)-2,3-dihydro-[1,4] dioxino[2,3-h]-isoquinolin-10 (9H)-one (3…”

Section: General Procedures For the Preparation Of 3 B And 3 F-3 Nmentioning

confidence: 99%

Synthesis and Structure‐Activity Relationships of 3‐Arylisoquinolone Analogues as Highly Specific hCES2A Inhibitors

et al. 2020

Self Cite

View full text Add to dashboard Cite

Mammalian carboxylesterases (CES) are key enzymes that participate in the hydrolytic metabolism of various endogenous and exogenous substrates. Human carboxylesterase 2A (hCES2A), mainly distributed in the small intestine and colon, plays a significant role in the hydrolysis of many drugs. In this study, 3‐arylisoquinolones 3 h [3‐(4‐(benzyloxy)‐3‐methoxyphenyl)‐7,8‐dimethoxyisoquinolin‐1(2H)‐one] and 4 a [3‐(4‐(benzyloxy)‐3‐methoxyphenyl)‐4‐bromo‐7,8‐dimethoxyisoquinolin‐1(2H)‐one] were found to have potent inhibitory effects on hCES2A (IC50=0.68 μΜ, Ki=0.36 μΜ) and excellent specificity (more than 147.05‐fold over hCES1 A). Moreover, 4 a exhibited threefold improved inhibition on intracellular hCES2A in living HepG2 cells relative to 3 h, with an IC50 value of 0.41 μΜ. Results of inhibition kinetics studies and molecular docking simulations demonstrate that both 3 h and 4 a can bind to multiple sites on hCES2A, functioning as mixed inhibitors. Structure−activity relationship analysis revealed that the lactam moiety on the B ring is crucial for specificity towards hCES2A, while a benzyloxy group is optimal for hCES2A inhibitory potency; the introduction of a bromine atom may enhance cell permeability, thereby increasing the intracellular hCES2A inhibitory activity.

show abstract

“…These derivatives were prepared from O -substituted 3-arylisoquinolines via [2,3] or [3,3] rearrangement8. The conversion of acetal O -substituents to 2′-hydroxyl-1′-methoxylethyl N -substituents was promoted by dilute hydrochloric acid, which is distinct from the reported [2,3] rearrangements9.…”

mentioning

confidence: 99%

Regioselectivity and Mechanism of Synthesizing N-Substituted 2-Pyridones and 2-Substituted Pyridines via Metal-Free C-O and C-N Bond-Cleaving of Oxazoline[3,2-a]pyridiniums

Xue

Yang

et al. 2017

Sci Rep

Self Cite

View full text Add to dashboard Cite

Novel intermediate oxazoline[3,2-a]pyridiniums were facilely prepared from 2-(2,2-dimethoxyethoxy)-pyridines via acid promoted intramolecular cyclization. Sequentially, the quaternary ammonium salts were treated with different nucleophiles for performing regioselective metal-free C-O and C-N bond-cleaving to afford prevalent heterocyclic structures of N-substituted pyridones and 2-substituted pyridines. The reaction mechanism and regioselectivity were then systematically explored by quantum chemistry calculations at B3LYP/6-31 g(d) level. The calculated free energy barrier of the reactions revealed that aniline and aliphatic amines (e.g., methylamine) prefer to attack C8 of intermediate 4a, affording N-substituted pyridones, while phenylmethanamine, 2-phenylethan-1-amine and 3-phenylpropan-1-amine favor to attack C2 of the intermediate to form 2-substituted pyridines. With the optimized geometries of the transition states, we found that the aromatic ring of the phenyl aliphatic amines may form cation-π interaction with the pyridinium of the intermediates, which could stabilize the transition states and facilitate the formation of 2-substituted pyridines.

show abstract

Discovery of N-substituted 3-arylisoquinolone derivatives as antitumor agents originating from O-substituted 3-arylisoquinolines via [2,3] or [3,3] rearrangement

Cited by 11 publications

References 15 publications

Advances in the study of berberine and its derivatives: a focus on anti-inflammatory and anti-tumor effects in the digestive system

Advances in the study of berberine and its derivatives: a focus on anti-inflammatory and anti-tumor effects in the digestive system

Synthesis and Structure‐Activity Relationships of 3‐Arylisoquinolone Analogues as Highly Specific hCES2A Inhibitors

Regioselectivity and Mechanism of Synthesizing N-Substituted 2-Pyridones and 2-Substituted Pyridines via Metal-Free C-O and C-N Bond-Cleaving of Oxazoline[3,2-a]pyridiniums

Contact Info

Product

Resources

About