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A Novel Benzocoumarin-Stilbene Hybrid as a DNA ligase I inhibitor with in vitro and in vivo anti-tumor activity in breast cancer models
- Source :
- Scientific Reports, Scientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
- Publication Year :
- 2016
-
Abstract
- Existing cancer therapies are often associated with drug resistance and toxicity, which results in poor prognosis and recurrence of cancer. This necessitates the identification and development of novel therapeutics against existing as well as novel cellular targets. In this study, a novel class of Benzocoumarin-Stilbene hybrid molecules were synthesized and evaluated for their antiproliferative activity against various cancer cell lines followed by in vivo antitumor activity in a mouse model of cancer. The most promising molecule among the series, i.e. compound (E)-4-(3,5-dimethoxystyryl)-2H-benzo[h]chromen-2-one (19) showed maximum antiproliferative activity in breast cancer cell lines (MDA-MB-231 and 4T1) and decreased the tumor size in the in-vivo 4T1 cell-induced orthotopic syngeneic mouse breast cancer model. The mechanistic studies of compound 19 by various biochemical, cell biology and biophysical approaches suggest that the compound binds to and inhibits the human DNA ligase I enzyme activity that might be the cause for significant reduction in tumor growth and may constitute a promising next-generation therapy against breast cancers.
- Subjects :
- 0301 basic medicine
DNA damage
lcsh:Medicine
Antineoplastic Agents
Apoptosis
Breast Neoplasms
Biology
Pharmacology
Article
03 medical and health sciences
DNA Ligase ATP
Mice
Breast cancer
In vivo
Cell Line, Tumor
Stilbenes
medicine
Animals
Humans
Enzyme Inhibitors
lcsh:Science
Cell Proliferation
chemistry.chemical_classification
Anthracenes
DNA ligase
Multidisciplinary
Molecular Structure
Cell growth
lcsh:R
Cancer
Cell Cycle Checkpoints
medicine.disease
Xenograft Model Antitumor Assays
In vitro
Disease Models, Animal
030104 developmental biology
chemistry
lcsh:Q
Female
DNA Damage
Signal Transduction
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 7
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific reports
- Accession number :
- edsair.doi.dedup.....cc5da6ed1622c02c78d19c98ce647d81