Design, synthesis and evaluation of novel indole derivatives as AKT inhibitors

Yang, Dezhi; Wang, Peng; Liu, Jianzhen; Xing, Hualu; Liu, Yang; Xie, Wencheng; Zhao, Guisen

doi:10.1016/j.bmc.2013.11.022

Cited by 17 publications

(10 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Commercially available intermediates 16(a~c) was amino acid. Intermediate 18 was obtained by previous work . 16(a~c) reacted with thionyl chloride in methanol solution generating their methyl esters which were then treated with di‐tert‐butyl dicarbonate to afford the desired t ‐butyloxy carbonyl protection of amino esters, subsequently, which were reduced by lithium aluminum hydride producing chiral alcohol 17(a~c).…”

Section: Methodsmentioning

confidence: 99%

“…In our previous work, compound 1 (Figure ) was discovered via a screening of our self‐established library which exhibited very low activity against Akt1 with inhibition rate of 11.6%, at a concentration of 10 n m . Replacing benzyloxy group with 2‐aminoethoxy group at the 4‐position of compound 1 gave compound 2 which exhibited nearly fourfold higher inhibitory activity against Akt1 than compound 1 with inhibition rate of 48.6% . This suggested that the structural modification at the 4‐position of compound 1 probably is an efficient way to enhance activity against Akt1.…”

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

Design, synthesis, and evaluation of novel Akt1 inhibitors based on an indole scaffold

et al. 2017

Self Cite

View full text Add to dashboard Cite

A new series of potential Akt1 inhibitors with indole scaffold were designed and synthesized. The antiproliferative activity against PC-3 cell line and enzyme inhibitory activity against Akt1 were evaluated. Among them, some compounds showed much more potent antiproliferative activity and stronger Akt1 inhibitory activity compared to the positive control of GSK690693. In particular, compound 19b exhibited the most potent inhibitory activity against Akt1 with inhibition rate of 70.3% at a concentration of 10 nm. Furthermore, compound 19b could dose dependently reduce the phosphorylation of the downstream GSK3β protein in the PC-3 cell line and displayed fivefold higher antiproliferative activity against PC-3 cell line with IC value of 3.1 ± 0.1 μm than positive control (15.5 ± 0.4 μm). Herein, compound 19b may serve as a promising lead for further optimization and development of novel Akt1 inhibitors based on an indole scaffold.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Design, synthesis, and evaluation of novel Akt1 inhibitors based on an indole scaffold

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…Additionally, novel synthetic indole-chalcone fibrates exhibit antidyslipidaemic effects in hyperlipidaemic rats (Yang et al, 2014).…”

Section: What Is the Clinical Significancementioning

confidence: 99%

A chalcone derivative, 1m‐6, exhibits atheroprotective effects by increasing cholesterol efflux and reducing inflammation‐induced endothelial dysfunction

Chen

Tsai

Tsao

et al. 2020

British J Pharmacology

View full text Add to dashboard Cite

Background and Purpose: Atherosclerosis, resulting from lipid dysregulation and vascular inflammation, causes atherosclerotic cardiovascular disease (ASCVD), which contributes to morbidity and mortality worldwide. Chalcone and its derivatives possess beneficial properties, including anti-inflammatory, antioxidant and antitumour activity with unknown cardioprotective effects. We aimed to develop an effective chalcone derivative with antiatherogenic potential. Experimental Approach: Human THP-1 cells and HUVECs were used as in vitro models. Western blots and real-time PCRs were performed to quantify protein, mRNA and miRNA expressions. The cholesterol efflux capacity was assayed by 3 H labelling of cholesterol. LDL receptor knockout (Ldlr −/−) mice fed a high-fat diet were used as an in vivo atherogenesis model. Haematoxylin and eosin and oil red O staining were used to analyse plaque formation.

show abstract

“…The cytotoxic [ 13 , 14 , 15 , 16 ] and anticancer potency of substituted indole compounds was also proven. In this field they act as inhibitors of serine/threonine kinase (AKT) [ 17 ], tyrosinase [ 18 ], human sirtuins SIRT1-3 [ 19 ] or transcription factors NF-kB activation [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of Novel Indole-Derived Thioureas

et al. 2018

View full text Add to dashboard Cite

A series of 2-(1H-indol-3-yl)ethylthiourea derivatives were prepared by condensation of 2-(1H-indol-3-yl)ethanamine with appropriate aryl/alkylisothiocyanates in anhydrous media. The structures of the newly synthesized compounds were confirmed by spectroscopic analysis and the molecular structures of 8 and 28 were confirmed by X-ray crystallography. All obtained compounds were tested for antimicrobial activity against Gram-positive cocci, Gram-negative rods and for antifungal activity. Microbiological evaluation was carried out over 20 standard strains and 30 hospital strains. Compound 6 showed significant inhibition against Gram-positive cocci and had inhibitory effect on the S. aureus topoisomerase IV decatenation activity and S. aureus DNA gyrase supercoiling activity. Compounds were tested for cytotoxicity and antiviral activity against a large panel of DNA and RNA viruses, including HIV-1 and other several important human pathogens. Interestingly, derivative 8 showed potent activity against HIV-1 wild type and variants bearing clinically relevant mutations. Newly synthesized tryptamine derivatives showed also a wide spectrum activity, proving to be active against positive- and negative-sense RNA viruses.

show abstract

Design, synthesis and evaluation of novel indole derivatives as AKT inhibitors

Cited by 17 publications

References 25 publications

Design, synthesis, and evaluation of novel Akt1 inhibitors based on an indole scaffold

Design, synthesis, and evaluation of novel Akt1 inhibitors based on an indole scaffold

A chalcone derivative, 1m‐6, exhibits atheroprotective effects by increasing cholesterol efflux and reducing inflammation‐induced endothelial dysfunction

Synthesis and Biological Evaluation of Novel Indole-Derived Thioureas

Contact Info

Product

Resources

About