DNA intercalators based on (1,10-phenanthrolin-2-yl)isoxazolidin-5-yl core with better growth inhibition and selectivity than cisplatin upon head and neck squamous cells carcinoma

Autor: Antonio Rescifina, Giulia Monciino, Placido Mineo, Chiara Zagni, Venerando Pistarà, Emanuele Amata, Angelo Nicosia, Giuseppe Floresta, Maria Giulia Varrica, Antonio Abbadessa, Rogerio M. Castilho
Rok vydání: 2018
Předmět:
Models
Molecular
Oncology
Circular dichroism
01 natural sciences
HeLa
3-Dipolar cycloaddition
chemistry.chemical_compound
Drug Discovery
Molecular Structure
biology
Chemistry
DNA
Neoplasm
General Medicine
1
3-Dipolar cycloaddition
DNA-intercalators
Head and neck squamous cells carcinoma
Isoxazolidines
Pharmacology
Drug Discovery3003 Pharmaceutical Science
Organic Chemistry
Intercalating Agents
Head and Neck Neoplasms
Carcinoma
Squamous Cell
Growth inhibition
medicine.drug
medicine.medical_specialty
Cell Survival
Antineoplastic Agents
010402 general chemistry
Structure-Activity Relationship
Cell Line
Tumor
Internal medicine
medicine
Carcinoma
Humans
Cell Proliferation
Cisplatin
Dose-Response Relationship
Drug
Squamous Cell Carcinoma of Head and Neck
010405 organic chemistry
Isoxazoles
biology.organism_classification
medicine.disease
Molecular biology
Binding constant
0104 chemical sciences
Docking (molecular)
Drug Screening Assays
Antitumor
DNA
Zdroj: European Journal of Medicinal Chemistry. 143:583-590
ISSN: 0223-5234
DOI: 10.1016/j.ejmech.2017.11.067
Popis: ((3RS,5SR)- and ((3RS,5RS)-2-(2-methoxybenzyl)-3-(1,10-phenanthrolin-2-yl)isoxazolidin-5-yl)methanol have been synthesized, according to 1,3-dipolar cycloaddition methodology, as DNA intercalating agents and evaluated for their anticancer activity against human cervical carcinoma HeLa and head and neck squamous cells carcinoma cell lines. The synthesized compounds exhibited good cytotoxic activity with IC50 better than cisplatin, used as the main and effective treatment for HNSCC, and a 24.3–72.0-fold selectivity respect to the 184B5 non-cancerous immortalized breast epithelial cell lines. Unwinding assay, circular dichroism data, and Uv-vis melting experiments confirmed that these compounds act as DNA intercalators with a binding constant in the order of 104 M−1. Docking studies showed that both compounds can interact as intercalating agent with both poly-d(AT)2 and poly-d(GC)2, preferring an entrance by the minor groove of the poly-d(AT)2.
Databáze: OpenAIRE
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