C‐(2‐Chloroquinoline‐3‐yl)‐N‐phenyl Nitrone: New Synthetic Antioxidant Inhibits Proliferation and Induces Apoptosis of Breast Carcinoma MCF‐7 Cells

Abstract

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.

Tumor Necrosis Factor‐α and Apoptosis Signal‐Regulating Kinase 1 Control Reactive Oxygen Species Release, Mitochondrial Autophagy and C‐Jun N‐Terminal Kinase/P38 Phosphorylation During Necrotizing Enterocolitis

“…PBN is widely used for ROS scavenging, and most importantly, has been shown to reverse the age-related oxidative changes and to reduce oxidative damage from ischemia/reperfusion injury 40–44. The antioxidant activity of PBN protects biologically important molecules from oxidative damage.…”

“…PBN is one of the most widely used spin-trapping compounds that target mitochondrial ROS to reverse age-related oxidative changes and to alleviate oxidative damage from ischemia/ reperfusion injury 40–44. RIE-1 (2 × 10 4 ) cells were incubated with 0.5 mM PBN for 2 h at 37°C.…”

Novel quinoline derivatives carrying nitrones/oximes nitric oxide donors: Design, synthesis, antiproliferative and caspase-3 activation activities

“…Compounds 6c, 6e, and 6f exhibited higher potency as anticancer agents compared to doxorubicin, with IC 50 ranging from 0.45 to 0.91 μM. [33] Incorporation of biologically active moieties into quinoline such as nitrones [34] and oximes [35] may produce biologically active anticancer agents.Compound III showed significant anticancer activity with IC 50 of 31.42 μM against Hep-G 2 cancer cell line (Figure 1). Compound 6e exhibited more pre-G1 apoptosis and cell cycle arrest at the G2/M phase than in other phases.…”

“…A remarkable overexpression of caspase-3 protein levels was observed in cells treated with the tested compounds. [34] Nitrones are a Arch Pharm Chem Life Sci. K E Y W O R D S antiproliferative, apoptosis, caspase 3, nitric oxide, nitrones, oximes 1 | INTRODUCTION Quinoline is a significant nucleus which has attracted the attention of medicinal chemists due to its variable pharmacological activities.…”

“…[31] Compound II exhibits remarkable anticancer activity against HL60 cancer cell line with IC 50 of 0.68 μM (Figure 1). [33] Incorporation of biologically active moieties into quinoline such as nitrones [34] and oximes [35] may produce biologically active anticancer agents.…”