Preparation and evaluation of a set of bis(methoxycarbonylmethylthio) heteroquinones as CDC25B phosphatase inhibitors

Abstract

A set of new heteroquinone derivatives bearing two methoxycarbonylmethylthio groups on the benzoquinone ring were synthesized and evaluated for CDC25B phosphatase inhibitory activity. All compounds inhibited the enzyme with IC50 values in the micromolar range regardless of the size and heteroatoms constituting the heterocycle fused to the quinone ring. Moreover, these quinonoid-based compounds showed moderate antiproliferative activity toward two cancer cell lines (HeLa and MiaPaca-2). These results provide additional data for CDC25 inhibition by quinone-type derivatives and highlight the importance of substituents on the quinonic moiety.Heterocyclic quinones CDC25B inhibitors Enzymatic activity Phosphatase Cancer Cell cycle

A Comprehensive Overview of the Developments of Cdc25 Phosphatase Inhibitors

“…The malonic acid derivative 12 did not show the expected rise of the activity with IC 50 value 10.7 ± 0.5 µM on Cdc25B and displayed moderate cytotoxicities against the HeLa cell line [32], whereas compound 13 exhibited IC 50 of 4.55 ± 0.16 µM toward Cdc25B and weak activity against HeLa cell lines [32]. Bis(methoxycarbonylmethylthio)heteroquinone analog of vitamin K 3 14 showed reasonable activity against Cdc25B with IC 50 of 1.17 ± 0.04 µM [33].…”

“…Dimethyl 2,2 -((5,8-dioxo-5,8-dihydroquinoline-6,7-diyl)bis(sulfanediyl)) diacetate ( 27) showed IC 50 of 1.63 ± 0.21 µM on Cdc25B. In addition, 27 showed inhibition percent of 79 ± 0.9 and 77 ± 2.1% at 100 µM toward HeLa and MiaPaCa-2 cell lines, respectively, while at 10 µM it showed an inhibition of 13 ± 0.9 and 24 ± 15.4% against the same cell lines, respectively [33].…”

An efficient method for the synthesis of 6,7-bis(alkylthio- or alkylamino-substituted)quinoline-5,8-diones via nucleophilic addition/oxidation of alkylthio and alkylamino derivatives to quinoline-5,8-dione

“…Quinolinequinones have shown promise in possible anti-tumor, [1][2][3][4] anti-cancer, 5 anti-bacterial, 6 trypanocidal, 7 anti-tuberculosis, 8 anti-inflammatory, 9 anti-malarial agents, 10 and anti-fungal. 11 Scheme 1.…”

Synthetic and Biological Utility of 2,3-Dichloro-1,4-Naphthoquinone: A Review

“…The formation of diquinonylamines (86) [40] and an amine substituted analog (88) [41] were reported while 2,3-dichloro-1,4-naphthoquinone (1) reacted with benzotriazole (89) and aliphatic or aromatic amines to give the corresponding 2-amino-3-(benzotriazol-1-yl)-1,4-naphthoquinones (90) [42].…”