C-(2-chloroquinoline-3-yl)-N-phenyl nitrone: new synthetic antioxidant inhibits proliferation and induces apoptosis of breast carcinoma MCF-7 cells.
In this work, a new quinoline nitrone derivative, C-(2-chloroquinoline-3-yl)-N-phenyl nitrone (CQPN) was successfully prepared and proved by spectral analysis. The antioxidant activity of CQPN against various radicals was investigated and its anti-cancer properties against different human tumor cell lines including the solid tumor cell lines hepatocarcinoma (Hep-G2) and breast carcinoma (MCF-7); the hematopoietic tumor cell line lymphoblastic leukemia (1301) was also explored. CQPN activities were compared to that of the known nitrone C-phenyl-N-tert-butyl nitrone (PBN). Our results showed that although PBN was the stronger antioxidant than CQPN, the latter was an effective scavenger of different non-physiological (1,1-diphenyl-2-picrylhyrazyl) and physiological (peroxyl and hydroxyl) radicals. Both of CQPN and PBN possess a significant inhibitory property against LPS-stimulated NO production in macrophage. CQPN and PBN treatment resulted in a growth inhibition in Hep-G2 cells (IC50 31.42 microM and 18.6 microM, respectively). Unlike PBN, CQPN strongly inhibited the growth of MCF-7 cells (IC50 14.01 microM) in a dose-dependent manner. On contrary, CQPN and PBN exhibited a proliferative stimulatory activity of the immune cells including macrophages and lymphocytes. Exploring the cytotoxic effect of CQPN against MCF-7 cells indicated that CQPN led to a major time-dependent disturbance in the cell-cycle phases including progressive arrest in both S- and G2/M-phases. This disturbance was found to be associated with a kinetic induction of apoptosis. The novel nitrone derivative CQPN is a strong antioxidant, though less than PBN, and it may be an effective anti-proliferative compound against breast carcinoma.
Ramadan
Mohamed
M
Department of Medicinal Chemistry, Faculty of Pharmacy, El-Minia University, El-Minia, Egypt.
Gamal-Eldeen
Amira M
AM
Abdel-Aziz
Mohamed
M
Abuo-Rahma
Gamal el-Din
Gel-D
Abdel-Nabi
Hisham
H
Nagib
Abdel-Hamid
AH
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D000975:Antioxidants / Q000138:chemical synthesis* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy*; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D006801:Humans; D009589:Nitrogen Oxides / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D000975:Antioxidants; D009589:Nitrogen Oxides; D011804:Quinolines; C015388:nitrones