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Design, synthesis, computational and biological evaluation of novel hydroxamic and carboxylic acid derivatives as histone decaetylase inhibitors

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Title Statement Design, synthesis, computational and biological evaluation of novel hydroxamic and carboxylic acid derivatives as histone decaetylase inhibitors
 
Added Entry - Uncontrolled Name Gharia, Bhavini ; Department of Pharmaceutical Chemistry, Maliba Pharmacy College, UkaTarsadia University, Bardoli 394 350, India
Suhagia, Bhanubhai N; Department of Pharmaceutical Chemistry, Dharamsinh Desai University, Nadiad 387 001, India
Upadhyay, Jagat kumar; Department of Pharmaceutical Chemistry, Dharamsinh Desai University, Nadiad 387 001, India
Champaneria, Richa ; Department of Pharmaceutical Chemistry, Maliba Pharmacy College, UkaTarsadia University, Bardoli 394 350, India
Lodha, Sandesh ; Department of Pharmaceutical Chemistry, Maliba Pharmacy College, UkaTarsadia University, Bardoli 394 350, India
Shah, Shailesh A; Department of Pharmaceutical Chemistry, Maliba Pharmacy College, UkaTarsadia University, Bardoli 394 350, India
 
Uncontrolled Index Term Hydroxamic acid derivatives, carboxylic acid derivatives, anticancer agents, 1,3,4-thiadiazoles,computational study
 
Summary, etc. <p>One of the recent targets is histone deacetylase (HDAC) which provide a very promising new approach for anticancer drugs, which may combine clinical efficacy with relatively mild toxicological side effects. Modification of histone acetylation level, promoted by histone acetylase (HAT) and HDAC enzyme, has been recognize to play an important role in epigenetic modulation of gene expression, so HDAC inhibitors are considered a new class of anticancer agents. A new series of hydroxamic and carboxylic acid analogues based on the 1,3,4-thiadiazole scaffold has been designed and synthesized with the aim of exploring its potential as new antitumor agents. Biological results have revealed that the structural modifications proposed significantly affected inhibitory potency as well as selectivity for HDAC inhibitors. Most target compounds are significantly more active, specifically <strong>5a</strong>, <strong>5b</strong>, <strong>5e</strong> with IC<sub>50</sub> values in the low micromolar or, the most active compounds in the series. Selected compounds have been tested on the viability of MDA-MB-231 (breast cancer cell) and K562 (chronic myelogenous leukemia cell), A549 (human lung cancer), PC3 (Prostate cancer cell lines) using MTT assay. Docking simulations suggested that the most active compounds can recognize the binding site (PDB Code 1w22 reference compound) using a similar interactions network. These results have allowed us to rationalize the observed structure–activity relationships.</p>
 
Publication, Distribution, Etc. Indian Journal of Chemistry -Section B (IJC-B)
2021-01-21 15:51:21
 
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http://op.niscair.res.in/index.php/IJCB/article/view/45471
 
Data Source Entry Indian Journal of Chemistry -Section B (IJC-B); ##issue.vol## 59, ##issue.no## 05 (2020): Indian Journal of Chemistry Section - B (IJCB)
 
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