5‐Arylidene‐2‐(4‐hydroxyphenyl)aminothiazol‐4(5H)‐ones with selective inhibitory activity against some leukemia cell lines

Abstract

The data on the pharmacology of 4‐thiazolidinones showed that 5‐ene‐2‐(imino)amino‐4‐thiazolidinones are likely to comprise one of the most promising groups of compounds possessing anticancer properties. A series of 5‐arylidene‐2‐(4‐hydroxyphenyl)aminothiazol‐4(5H)‐ones was designed, synthesized, and studied against 10 leukemia cell lines, including the HL‐60, Jurkat, K‐562, Dami, KBM‐7, and some Ba/F3 cell lines. The structure–activity relationship analysis shows that almost all tested 5‐arylidene‐2‐(4‐hydroxyphenyl)aminothiazol‐4(5H)‐ones were characterized by ІС50 values lower or comparable to that of the control drug chlorambucil. Among the tested compounds, (5Z)‐5‐(2‐methoxybenzylidene)‐ (12), (5Z)‐(2‐ethoxybenzylidene)‐ (21), (5Z)‐5‐(2‐benzyloxybenzylidene)‐ (25), and (5Z)‐5‐(2‐allyloxybenzylidene)‐2‐(4‐hydroxyphenylamino)thiazol‐4(5H)‐ones (28) possessed the highest antileukemic activity at submicromolar concentrations (ІС50 = 0.10–0.95 µM).

Anticancer 5‐arylidene‐2‐(4‐hydroxyphenyl)aminothiazol‐4(5H)‐ones as tubulin inhibitors

“…The syntheses of compounds 1-12 (Figure 1) were described in our previous reports. [9,10,22] The InChI codes of the investigated compounds, together with some biological activity data, are provided as Supporting Information.…”

“…[ 9 ] Moreover, our in‐depth study of 5‐arylidene‐2‐(4‐hydroxyphenylamino)thiazol‐4(5 H )‐ones antiproliferative activity against a panel of leukemic cell lines (Ba/F3 parental; Ba/F3‐MPL CALR del52; Ba/F3‐MPL CALR WT; Ba/F3‐MPL CALR ins5; KBM7‐SLF N233; KBM7_WT; Dami; HL‐60; Jurkat and K‐562) showed micro‐ and submicromolar ranges of IC 50 values that were comparable with control drug chlorambucil. [ 10 ]…”

“…[9] Moreover, our in-depth study of 5-arylidene-2-(4-hydroxyphenylamino)thiazol-4(5H)-ones antiproliferative activity against a panel of leukemic cell lines (Ba/F3 parental; Ba/F3-MPL CALR del52; Ba/F3-MPL CALR WT; Ba/F3-MPL CALR ins5; KBM7-SLF N233; KBM7_WT; Dami; HL-60; Jurkat and K-562) showed micro-and submicromolar ranges of IC 50 values that were comparable with control drug chlorambucil. [10] At the same time, very few attempts were made to outline the main molecular modes of action of 5-ene-2-amino(imino)-4thiazolidinones. [1,11] Analysis of the molecular mechanisms of their action allowed us to identify the main involved pathways: induction of apoptosis, cell cycle arrest, [12][13][14][15] PPAR (peroxisome proliferatoractivated receptor)-related pathways, [16,17] inhibition of necroptosis, [18,19] and modulation of Red/Ox signaling and reactive oxygen species (ROS) production.…”

Anticancer cytotoxicity of indole-thiazolidinone hybrids, in silico study of mechanisms of their action

“…Another direction of search for possible anticancer agents among 4-thiazolidinones is represented by the study of a series of 5-arylidene-2-arylaminothiazol-4(5H)-ones on a panel of leukemic cell lines that revealed hitcompounds with IC 50 values comparable with those for the control drug Chlorambucil. SAR analysis data showed a high impact of small methoxy and ethoxy groups at position 2 of the benzylidene ring of 5-arylidene-2-arylaminothiazol-4(5H)-ones on the antileukemic activity [10]. Thus, here we aimed at the direc ted structure-based design and synthesis of new hybrid molecules containing [6+5]-heterocycles and thiazolidine ring as potent anticancer agents (Fig.…”

The Bioactivity of Thiazolidin-4-Ones: A Short Review of the Most Recent Studies

“…The Compound 26c showed strong cytotoxic activity against three Ba/F3 cell lines at IC 50 values in the range of 0.10-0.24 µM and against Dami cell line (IC 50 = 0.87 µM). The Compound 26i, with 2-allyloxy substituent, possessed the highest antileukemic activity against Dami, HL-60, Jurkat and K-562 cell lines at submicromolar concentration 0.95, 0.17, 0.10 and 0.18, respectively [40].…”