dc.contributor.author |
Kassab, SE |
|
dc.contributor.author |
Mowafy, S |
|
dc.contributor.author |
Alserw, AM |
|
dc.contributor.author |
Seliem, JA |
|
dc.contributor.author |
El-Naggar, SM |
|
dc.contributor.author |
Omar, NN |
|
dc.contributor.author |
Awad, MM |
|
dc.date.accessioned |
2019-11-22T07:59:39Z |
|
dc.date.available |
2019-11-22T07:59:39Z |
|
dc.date.issued |
2019-01 |
|
dc.identifier.issn |
1475-6366 |
|
dc.identifier.other |
https://doi.org/ |
|
dc.identifier.uri |
https://www.ncbi.nlm.nih.gov/pubmed/31072216 |
|
dc.description |
Accession Number: WOS:000467713900001 |
en_US |
dc.description.abstract |
Histone deacetylase 6 (HDAC6) is an attractive target for cancer therapeutic intervention. Selective HDAC6 inhibitors is important to minimise the side effects of pan inhibition. Thus, new class of hydroxamic acid-based derivatives were designed on structural basis to perform preferential activity against HDAC6 targeting solid tumours. Interestingly, 1-benzylbenzimidazole-2-thio-N-hydroxybutanamide 10a showed impressive preference with submicromolar potency against HDAC6 (IC50 = 510 nM). 10a showed cytotoxic activity with interesting profile against CCHE-45 at (IC50 = 112.76 mu M) when compared to standard inhibitor Tubacin (IC50 = 20 mu M). Western blot analysis of acetylated-alpha-tubulin verified the HDAC6 inhibiting activity of 10a. Moreover, the insignificant difference in acetylated-alpha-tubulin induced by 10a and Tubacin implied the on-target cytotoxic activity of 10a. Docking of 10a in the binding site of HDAC6 attributed the activity of 10a to pi-pi stacking with the amino acids of the hydrophobic channel of HDAC6 and capture of zinc metal in bidentate fashion. The therapeutic usefulness besides the on-target activity may define 10a as an interesting safe-lead inhibitor for future development. |
en_US |
dc.description.uri |
https://www.scimagojr.com/journalsearch.php?q=17605&tip=sid&clean=0 |
|
dc.language.iso |
en_US |
en_US |
dc.publisher |
TAYLOR & FRANCIS LTD |
en_US |
dc.relation.ispartofseries |
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY;Volume: 34 Issue: 1 Pages: 1062-1077 |
|
dc.relation.uri |
https://cutt.ly/beX0SCh |
|
dc.subject |
EPIGENETICS |
en_US |
dc.subject |
DEXAMETHASONE |
en_US |
dc.subject |
TUBULIN |
en_US |
dc.subject |
DERIVATIVES |
en_US |
dc.subject |
ACETYLATION |
en_US |
dc.subject |
RICOLINOSTAT |
en_US |
dc.subject |
PROTEIN |
en_US |
dc.subject |
COMBINATION |
en_US |
dc.subject |
LIGAND BOND LENGTHS |
en_US |
dc.subject |
HISTONE DEACETYLASE 6 |
en_US |
dc.subject |
cytotoxicity |
en_US |
dc.subject |
choroid plexus carcinoma |
en_US |
dc.subject |
acute promyeloblastic leukemia |
en_US |
dc.subject |
benzimidazole |
en_US |
dc.subject |
on-target activity |
en_US |
dc.subject |
acetylated-alpha-tubulin |
en_US |
dc.subject |
Preferential HDAC6 inhibitor |
en_US |
dc.title |
Structure-based design generated novel hydroxamic acid based preferential HDAC6 lead inhibitor with on-target cytotoxic activity against primary choroid plexus carcinoma |
en_US |
dc.type |
Article |
en_US |
dc.identifier.doi |
https://doi.org/ |
|
dc.Affiliation |
October University for modern sciences and Arts (MSA) |
|