Design, synthesis and antiproliferative activity of hydroxyacetamide derivatives against HeLa cervical carcinoma cell and breast cancer cell line

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- (-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 substituted oxazolone. 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 compared with the standard, adriamycin,

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“…interest, variants of interest and variants of high consequence 5 . In US, variants like B.1.1.7 (α), B.1.351 (β), B.1.617.2 (δ) and P.1 (γ) were concerned as variants of concern without any variants of high consequence 6,7 .…”

Design, in silico studies, and synthesis of new 1,8-naphthyridine-3-carboxylic acid analogues and evaluation of their H1R antagonism effects

“…Heterocyclic synthesis has become a powerful technique in organic synthesis for generating new molecules for drug discovery and development. [1][2][3][4][5][6][7][8] Nitrogen atom-containing heterocyclic compounds provide highly functionalized scaffolds on which pharmacophoric features can be arranged to obtain effective and selective drugs. [9][10][11][12][13][14][15][16][17] Histamine is one of the most important chemical mediators that inuences immune regulation via an acute and chronic inammatory response through 4 different types of G-protein coupled receptors, H1, H2, H3, and H4.…”

Antihyperglycemic Activity of Phenyl and Ortho-Hydroxy Phenyl Linked Imidazolyl Triazolo Hydroxamic Acid Derivatives

“…The synthesis of hydroxamic acid derivatives (FP1-FP12) were previously done by fusion of 2-chloro-N-hydroxyacetamide with 2- [4].…”

“…1). The previous study reflects that synthesized molecules (FP1-FP12) showed good HDAC inhibition and MCF-7 cell line inhibition [4], DPPH radical scavenging activity, anti-inflammatory and analgesic activity and brine shrimp lethality assay, antimicrobial and antifungal activity [5][6]. In this article, the anti-hyperglycemic activity of the synthesized molecules (FP1-FP12) was evaluated in streptozotocin-induced hyperglycemic rats.…”