Abstract
Purpose: To design and develop a new series of histone deacetylase inhibitors (FP1 - FP12) and evaluate their inhibitory activity against hydroxyacetamide (HDAC) enzyme mixture-derived HeLa cervical carcinoma cell and MCF-7.Methods: The designed molecules (FP1 - FP12) were docked using AUTODOCK 1.4.6. FP3 and FP8 showed higher interaction comparable to the prototypical HDACI. The designed series of 2-[[(3- Phenyl/substituted Phenyl-[4-{(4- (substituted phenyl)ethylidine-2-Phenyl-1,3-Imidazol-5-One}](-4H- 1,2,4-triazol-5-yl)sulfanyl]-N-hydroxyacetamide derivatives (FP1-FP12) was synthesized by merging 2- [(4-amino-3-phenyl-4H- 1, 2, 4-triazol-5-yl) sulfanyl]- N-hydroxyacetamide and 2-{[4-amino-3-(2- hydroxyphenyl)-4H-1,2, 4-triazol-5-yl]sulfanyl}-N hydroxyacetamide derivatives with aromatic substitutedoxazolone. The biological activity of the synthesized molecule (FP1-FP12) was evaluated against HDAC enzyme mixture-derived HeLa cervical carcinoma cell and breast cancer cell line (MCF-7).Results: HDAC inhibitory activity of FP10 showed higher IC50 (half-maximal concentration inhibitory activity) of 0.09 μM, whereas standard SAHA molecule showed IC50 of 0.057 μM. On the other hand, FP9 exhibited higher GI50 (50 % of maximal concentration that inhibited cell proliferation) of 22.8 μM against MCF-7 cell line, compared with the standard, adriamycin, with GI50 of (-) 50.2 μM.Conclusion: Synthesis, spectral characterization, and evaluation of HDAC inhibition activity and in vitro anticancer evaluation of novel hydroxyacetamide derivatives against MCF-7 cell line have been achieved. The findings indicate the emergence of potentialanticancer compounds.Keywords: Molecular docking, Hydroxyacetamide derivative, Histone deacetylase inhibition activity, MCF-7 cell line
Highlights
Histone deacetylase (HDAC) enzyme is one of the leading targets in the process of anticancer drug development
HDAC was divided into three distinct structural classes as class (I/II) zincdependent and class (111) NAD dependent [1]
histone deacetylase inhibitor (HDACI) induced cell cycle arrest and growth inhibition is usually correlated with transcriptional activation of p21WAF1/CIP1, p27KIP1, GADD45a [4] and inhibition of cyclin A, cyclin D and thymidylate synthetase [5]
Summary
Histone deacetylase (HDAC) enzyme is one of the leading targets in the process of anticancer drug development. The most important HDACI are the hydroxamic acids group followed by the benzamides, the cyclic tetra peptides, the carboxylic acids and the electrophilic ketones [6] These observations prompted us to modify the linker portion to an imidazolo triazolated moiety and enacting the metal binding hydroxamic acid portion and molecular docking against 1T69, synthesize and check their in vitro HDAC inhibition, antiproliferative efficacy against MCF-7 cell line. The mixture was stirred for 5 min and added drop wise to a previously prepared methanol solution of 0.0501 M, 2.81 g potassium hydroxide. Antiproliferative activity of FP1-FP12 was evaluated using Sulphorodamine B (SRB) assay method on MCF-7 cell line [14]. SRB assay results were linear with the number of cells and with values for cellular protein measured by both Lowry and Bradford assays at densities ranging from sparse sub-confluence to multilayered supraconfluence. Significant difference was set at p < 0.05
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
