Design and novel synthetic approach supported with molecular docking and biological evidence for naphthoquinone-hydrazinotriazolothiadiazine analogs as potential anticancer inhibiting topoisomerase-IIB

Samy Mohamady, Abdullah Ahmed Gibriel, Mahmoud Salama Ahmed, Moataz S. Hendy, Bassem H. Naguib

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

A novel synthetic approach was developed for the synthesis of 3-hydrazinotriazolothiadiazines in just one step from Purpald and phenacyl bromides. They were then selectively tethered to naphthoquinone fragments through hydrazine moiety generating novel Naphthoquinone-hydrazinotriazolothiadiazine analogues. In vitro cytotoxicity for the synthesized chemical entities was validated against HepG2 and MCF-7 cell lines and recorded IC50 inhibitory profile range of 0.07–19.68 µM and 1.19–67.32 µM respectively. Among the synthesized series, compound 4c had maximal cytotoxicity against HepG2 and was therefore selected for further downstream biological investigations. Caspase 3 apoptotic marker was significantly upregulated in cells treated with compound 4c with induction of apoptosis at Pre-G1 phase and cell death at G2/M phase. Compounds 4a, 4c and 4d exhibited the most powerful inhibitory range (0.55–0.64 µM) against Topo IIB. Molecular docking study revealed potential interactions of those compounds within the ATP catalytic binding domain of Topo-IIB with high scores. In conclusion, the novel Naphthoquinone-hydrazinotriazolothiadiazine analogues could serve as promising anticancer agents through inhibition of Topoisomerase–IIB.

Original languageEnglish (US)
Article number103641
JournalBioorganic Chemistry
Volume96
DOIs
StatePublished - Mar 2020

Keywords

  • Cancer
  • HepG2
  • Hydrazino-triazolothiadiazine
  • MCF-7
  • Naphthoquinone
  • Topoisomerase II-B

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Drug Discovery
  • Organic Chemistry

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