DSpace Repository

Design, synthesis, and biological evaluation of novel quinazolin-4(3h)-one-based histone deacetylase 6 (hdac6) inhibitors for anticancer activity

Show simple item record

dc.contributor.author Murugesan, Sankaranarayanan
dc.date.accessioned 2025-03-11T08:50:43Z
dc.date.available 2025-03-11T08:50:43Z
dc.date.issued 2023-07
dc.identifier.uri https://www.mdpi.com/1422-0067/24/13/11044
dc.identifier.uri http://dspace.bits-pilani.ac.in:8080/jspui/handle/123456789/18315
dc.description.abstract A series of novel quinazoline-4-(3H)-one derivatives were designed and synthesized as histone deacetylase 6 (HDAC6) inhibitors based on novel quinazoline-4-(3H)-one as the cap group and benzhydroxamic acid as the linker and metal-binding group. A total of 19 novel quinazoline-4-(3H)-one analogues (5a–5s) were obtained. The structures of the target compounds were characterized using 1H-NMR, 13C-NMR, LC–MS, and elemental analyses. Characterized compounds were screened for inhibition against HDAC8 class I, HDAC4 class IIa, and HDAC6 class IIb. Among the compounds tested, 5b proved to be the most potent and selective inhibitor of HDAC6 with an IC50 value 150 nM. Some of these compounds showed potent antiproliferative activity in several tumor cell lines (HCT116, MCF7, and B16). Amongst all the compounds tested for their anticancer effect against cancer cell lines, 5c emerged to be most active against the MCF-7 line with an IC50 of 13.7 μM; it exhibited cell-cycle arrest in the G2 phase, as well as promoted apoptosis. Additionally, we noted a significant reduction in the colony-forming capability of cancer cells in the presence of 5c. At the intracellular level, selective inhibition of HDAC6 was enumerated by monitoring the acetylation of α-tubulin with a limited effect on acetyl-H3. Importantly, the obtained results suggested a potent effect of 5c at sub-micromolar concentrations as compared to the other molecules as HDAC6 inhibitors in vitro. en_US
dc.language.iso en en_US
dc.publisher MDPI en_US
dc.subject Pharmacy en_US
dc.subject Cancer en_US
dc.subject Histone deacetylase en_US
dc.subject Quinazoline-4-(3H)-one en_US
dc.subject Small-molecule inhibitors en_US
dc.title Design, synthesis, and biological evaluation of novel quinazolin-4(3h)-one-based histone deacetylase 6 (hdac6) inhibitors for anticancer activity en_US
dc.type Article en_US


Files in this item

Files Size Format View

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record

Search DSpace


Advanced Search

Browse

My Account