| Title |
Synthesis and cytotoxic activities of novel 4-methoxy-substituted and 5-methyl-substituted (3′S,4′S)-(-)-cis-khellactone derivatives that induce apoptosis via the intrinsic pathway
|
|---|---|
| Published in |
Drug Design, Development and Therapy, June 2017
|
| DOI | 10.2147/dddt.s131753 |
| Pubmed ID | |
| Authors |
Jingrun Chen, Junjie Liu, Dongxiao Cui, Chaoqun Yan, Liqiang Meng, Liqian Sun, Shurong Ban, Rui Ge, Taigang Liang, Qingshan Li |
| Abstract |
This study deals with the design and synthesis of a series of novel 4-methoxy-substituted and 5-methyl-substituted (3'S,4'S)-(-)-cis-khellactones. The newly synthesized compounds were characterized by (1)H nuclear magnetic resonance (NMR), (13)C-NMR, mass spectrometry, and elemental analysis. All the derivatives were subjected to in vitro cytotoxicity screening against HEPG-2 (human liver carcinoma), SGC-7901 (human gastric carcinoma), and LS174T (human colon carcinoma), by using the MTT assay. The results revealed that several of the 4-methoxy-substituted compounds exhibited potent cytotoxicity. Among these, compound 12e showed the highest activity against cancer cells which 50% inhibitory concentration (IC50) values were in the range of 6.1-9.2 μM with low toxicity on normal human hepatocyte. Preliminary investigation of possible mechanisms of action of compound 12e against HEPG-2 cells indicated possible induction of apoptosis, as determined by morphological observations and Annexin V/propidium iodide (PI) double staining, in addition to apparent dissipation of mitochondrial membrane potential (MMP), as measured by 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide (JC-1) staining in combination with the activation of caspase-9 and caspase-3 by Western blot analysis. Overall, the data suggest that compound 12e may be a promising potential anti-cancer agent that could act primarily by inducing apoptosis through the mitochondria-mediated intrinsic pathway in human hepatoma cells. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Australia | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 9 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 9 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 2 | 22% |
| Student > Bachelor | 1 | 11% |
| Unknown | 6 | 67% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 2 | 22% |
| Biochemistry, Genetics and Molecular Biology | 1 | 11% |
| Unknown | 6 | 67% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 12 July 2017.
All research outputs
#22,963,239
of 25,604,262 outputs
Outputs from Drug Design, Development and Therapy
#1,753
of 2,271 outputs
Outputs of similar age
#289,779
of 331,069 outputs
Outputs of similar age from Drug Design, Development and Therapy
#37
of 44 outputs
Altmetric has tracked 25,604,262 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,271 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.3. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 331,069 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 44 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.