Discovery, bioactivity and docking simulation of Vorinostat analogues containing 1,2,4-oxadiazole moiety as potent histone deacetylase inhibitors and antitumor agents

Cai, Jin; Wei, Hongtao; Hong, Kwon Ho; Wu, Xiaoqing; Zong, Xi; Cao, Meng; Wang, Peng; Li, Lushen; Sun, Chunlong; Chen, Bin; Zhou, Gaoxing; Chen, Junqing; Ji, Min

doi:10.1016/j.bmc.2015.04.028

Cited by 35 publications

(22 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Compound 6H demonstrated highest enzyme inhibitor activity, testifying it to be specific and good potentiator of HDAC. Our bioactivity predictions are in coherence with in vitro testing performed by Cai et al, 2015, who also showed the most favorable IC 50 value of 6H against HDACs.…”

Section: 1571 Voronistat Analogues As Potential Epigenetic Anti-tumosupporting

confidence: 57%

“…1, 2, 4-oxadiazole-containing Vorinostat analogues designed by Cai et al, 2015 formed the dataset of compounds for the present study (Table 1).…”

Section: Selection Of Compound Datasetmentioning

confidence: 99%

“…Table 1 shows the affinity (rerank) scores of various Vorinostat analogues of dataset1 along with the HDAC activity (IC 50 ) as assessed by the Cai et al (2015). Evident from the docking (rerank) scores, hydroxamate compound (Figure 2) and in addition showed optimal in vitro activity.…”

Section: Pharmacophoric Mappingmentioning

confidence: 99%

“…Structure activity studies have revealed that Vorinostat (and other HDACs as well) harbors Zn2+ binding group (ZBG), chelating Zn2+ at the bottom of the active binding site of HDACs; a hydrophobic linker occupying the long and narrow tubelike channel; a surface recognition group (cap), essential for recognizing and interacting with amino acid residues of the HDACs active site; and a polar connection unit (CU) linking "cap group" with the hydrophobic linker. The keen perusal at common pharmacophores of Vorinostat led to the development of novel HDAC inhibitors by Cai et al (2015). They synthesized series of HDAC inhibitors with 1, 2, 4-oxadiazole-containing Vorinostat analogues.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, in the view of given observation, the present study focuses on computer based pharmacological profiling, evaluation and identification of high affinity Vorinostat analogues from the dataset of compound synthesized by Cai et al (2015). In addition, a possible attempt has also been pursued to identify still better compound other than analogues from the present dataset through virtual screening approaches.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Pharmacological Analysis of Vorinostat Analogues as Potential Anti-tumor Agents Targeting Human Histone Deacetylases: an Epigenetic Treatment Stratagem for Cancers

Praseetha

Nayarisseri²,

Sureshkumar³

2016

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Alteration of the acetylation status of chromatin and other non-histone proteins by HDAC inhibitors has evolved as an excellent epigenetic strategy in treatment of cancers. The present study was sought to identify compounds with positive pharmacological profiles targeting HDAC1. Analogues of Vorinostat synthesized by Cai et al, 2015 formed the test compounds for the present pharmacological evaluation. Hydroxamte analogue 6H showed superior pharmacological profile in comparison to all the compounds in the analogue dataset owing to its better electrostatic interactions and hydrogen bonding patterns. In order to identify compounds with even better high affinity and pharmacological profile than 6H and Vorinostat, virtual screening was performed. A total of 83 compounds similar to Vorinostat and 154 compounds akin to analogue 6H were retrieved. SCHEMBL15675695 (PubCid: 15739209) and AKOS019005527 (PubCid: 80442147) similar to Vorinostat and 6H, were the best docked compounds among the virtually screened compounds. However, in spite of having good affinity, none of the virtually screened compounds had better affinity than that of 6H. In addition SCHEMBL15675695 was predicted to be a carcinogen while AKOS019005527 is Ames toxic. From, our extensive analysis involving binding affinity analysis, ADMET properties predictions and pharmacophoric mappings, we report Vorinostat hydroxamate analogue 6H to be a potential candidate for HDAC inhibition in treatment of cancers through an epigenetic strategy.

show abstract

Section: 1571 Voronistat Analogues As Potential Epigenetic Anti-tumosupporting

confidence: 57%

“…1, 2, 4-oxadiazole-containing Vorinostat analogues designed by Cai et al, 2015 formed the dataset of compounds for the present study (Table 1).…”

Section: Selection Of Compound Datasetmentioning

confidence: 99%

Section: Pharmacophoric Mappingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Pharmacological Analysis of Vorinostat Analogues as Potential Anti-tumor Agents Targeting Human Histone Deacetylases: an Epigenetic Treatment Stratagem for Cancers

Praseetha

Nayarisseri²,

Sureshkumar³

2016

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

show abstract

Access to Trifluoromethylketones from Alkyl Bromides and Trifluoroacetic Anhydride by Photocatalysis

Zeng

et al. 2023

Angewandte Chemie

View full text Add to dashboard Cite

Aliphatic trifluoromethyl ketones are a type of unique fluorine‐containing subunit which plays a significant role in altering the physical and biological properties of molecules. However, catalytic methods to provide direct access to aliphatic trifluoromethyl ketones is highly desirable yet remains underdeveloped, partially due to the high reactivity and instability of trifluoroacetyl radical. Herein, we report a photocatalytic synthesis of trifluoromethyl ketones from alkyl bromides with trifluoroacetic anhydride. The reaction features a dual catalysis of visible‐light and XAT reaction, followed by an enabling radical‐radical cross‐coupling of alkyl radical with a stabilized trifluoromethyl radical. The reaction provides the first straightforward access to aliphatic trifluoromethyl ketones from easily‐available and cost‐effective alkyl halides and TFAA.

show abstract

Access to Trifluoromethylketones from Alkyl Bromides and Trifluoroacetic Anhydride by Photocatalysis

Zeng

et al. 2023

Angew Chem Int Ed

View full text Add to dashboard Cite

show abstract

Discovery, bioactivity and docking simulation of Vorinostat analogues containing 1,2,4-oxadiazole moiety as potent histone deacetylase inhibitors and antitumor agents

Cited by 35 publications

References 43 publications

Pharmacological Analysis of Vorinostat Analogues as Potential Anti-tumor Agents Targeting Human Histone Deacetylases: an Epigenetic Treatment Stratagem for Cancers

Pharmacological Analysis of Vorinostat Analogues as Potential Anti-tumor Agents Targeting Human Histone Deacetylases: an Epigenetic Treatment Stratagem for Cancers

Access to Trifluoromethylketones from Alkyl Bromides and Trifluoroacetic Anhydride by Photocatalysis

Access to Trifluoromethylketones from Alkyl Bromides and Trifluoroacetic Anhydride by Photocatalysis

Contact Info

Product

Resources

About