Curcumin‘s antineoplastic, radiosensitizing and radioprotective properties

In this study, two chiral nitronyl nitroxyl radicals, L1 and D1, were synthesized and evaluated for their potential radioprotective properties invitro and invivo. We synthesized the new stable nitronyl nitroxide radicals, L1 and D1, according to Ullman’s method, and their chemical structures were characterized using UV-vis absorption, electron spin resonance (ESR), and circular dichroism (CD) spectra. The cytotoxicity of L1 and D1 on C6 glioma cells (C6 cells) was examined using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. To study the anti-radiation effects of L1 and D1 on C6 cells, we determined the optical density (OD) values of irradiated C6 cells using the MTT assay. The effects of L1 and D1 on the survival rate of mice after radiation exposure was evaluated. To demonstrate the influence of L1 and D1 pre-treatment on the antioxidant enzyme system, we studied the activities of superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and glutathione peroxidase (GSH) in mouse plasma after exposure to 6.5 Gy gamma radiation. The results showed that L1 and D1 did not have any obvious cytotoxicity at concentrations below 125μgmL−1. Moreover, L1 and D1 had the same cytotoxic effects on C6 cells. L1 and D1 significantly enhanced C6 cell survival after 8, 10, and 12 Gy radiation exposure, and there was no significant difference in the OD values between L1 and D1. The effects of these drugs on mouse survival rates were dose-dependent. Pre-treatment with different concentrations of L1, D1, or WR2721 significantly increased the activity of SOD, CAT, and GSH and significantly decreased the activity of MDA compared with radiation exposure only. In addition, the activities of SOD, CAT, and GSH in the L1 group were higher than those in the D1 group, whereas the activity of MDA was lower. Therefore, L1 and D1 have potential as safe and efficient therapeutic drugs against radiation damage.

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ChemInform Abstract: RADIOPROTECTIVE PROPERTIES OF THE MERCAPTOCAFFEINE DERIVATIVES

Chemischer Informationsdienst ◽

10.1002/chin.197534281 ◽

1975 ◽

Vol 6 (34) ◽

Author(s):

G. N. KRUTOVSKIKH ◽

M. B. KOLESOVA ◽

A. M. RUSANOV ◽

L. P. VARTANYAN ◽

M. G. SHAGOYAN

Keyword(s):

Radioprotective Properties

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Synthesis and radioprotective properties of linear and cyclic mercaptoethylamine analogs containing the CF3 group

Pharmaceutical Chemistry Journal ◽

10.1007/bf02333886 ◽

1996 ◽

Vol 30 (10) ◽

pp. 617-619

Author(s):

V. V. Znamenskii ◽

I. I. Grechka ◽

Yu. L. Ignatova ◽

N. M. Karimova

Keyword(s):

Radioprotective Properties

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Induction of acute phase proteins in mice and humans by treatment with AS101, an immunomodulator with radioprotective properties

Immunopharmacology ◽

10.1016/0162-3109(94)00054-j ◽

1995 ◽

Vol 29 (2) ◽

pp. 149-158 ◽

Cited By ~ 6

Author(s):

Yona Kalechman ◽

Adi Shani ◽

Michael Albeck ◽

Benjamin Sredni

Keyword(s):

Acute Phase ◽

Acute Phase Proteins ◽

Radioprotective Properties

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Bone Marrow Small Molecule Radioprotectors.

Blood ◽

10.1182/blood.v110.11.4096.4096 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4096-4096

Author(s):

Michael W. Epperly ◽

Darcy Franicola ◽

Tracy Dixon ◽

Xichen Zhang ◽

Paavani Komanduri ◽

...

Keyword(s):

Small Molecules ◽

Small Molecule ◽

Survival Curve ◽

Radiation Sensitivity ◽

Whole Body ◽

Linear Quadratic ◽

National Priority ◽

Radioprotective Properties

Abstract Development of small molecule radioprotectors is a major national priority. Two groups of compounds have particular promise. The first group targets the mitochondria based upon previous data with transgene MnSOD which when expressed in the mitochondria prevents apoptosis and increases radioprotection. These agents contain the antioxidant tempol or nitric oxide synthetase inhibitor 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT) attached to a hemi-gramicidin linker which targets the mitochondria. The second group consists of the dietary agent resveratrol and acetylated variants. Mouse hematopoietic progenitor 32Dcl3 cells were incubated for 1 hr in 10 μM tempol, AMT, or gramicidin linked tempol XJB-5-125 (tempol), XJB-7-75 (tempol) or JP4-039 (AMT). In separate experiments, 32Dcl3 cells were incubated for 1 hr in resveratrol or acetylated resveratrol. The cells were then irradiated to doses ranging from 0 to 8 Gy, plated in 0.8% methylcellulose, and incubated in a 5% CO2 incubator for 7 days. Colonies of greater than 50 cells were counted with the data analyzed using linear quadratic or single-hit, multi-target models. 32Dcl3 cells incubated in 10 μm tempol before irradiation resulted in no change in radiation sensitivity while incubation in XJB-5-125 or XJB-7-75 had decreased radiosensitivity. XJB-5-125 had an increased Do of 1.91 ± 0.67 Gy compared to 1.32 ± 0.09 Gy for 32Dcl3 cells incubated in tempol and 1.35 ± 0.27 Gy for control 32Dcl3 cells (p = 0.045 or 0.040, respectively). Incubation in XJB-5-75 resulted in an increased shoulder on the survival curve with an ñ of 19.4 ± 2.6 compared to 8.7 + 1.6 for cells incubated in tempol or 6.9 +1.8 for control 32Dcl3 cells (p = 0.025 or 0.022). Incubation in JP4-039 resulted in an increased Do of 2.2 ± 0.1 Gy compared to 1.24 ± 0.15 or 1.13 ± 0.06 for cells incubated in AMT or control 32Dcl3 cells only, respectively (p = 0.0115 or 0.0098, respectively). Incubation of 32Dcl3 cells in resveratrol or acetylated resveratrol before irradiation resulted in an increased shoulder on the survival curve of 33.2 ± 5.7 or 57.5 ± 9.9, respectively, compared to 6.9 ± 1.8 for 32Dcl3 cells (p = 0.0122 or 0.0072, respectively). These compounds were tested in mice receiving an LD50/30 irradiation dose. C57BL/6NHsd mice were injected intraperitoneally with 10 mg/kg of XJB-5-125, XJB-7-75or JP4-039 or 25 mg/kg of resveratrol or acetylated resveratrol and irradiated 10 mins later along with control mice to 9.5 Gy whole body irradiation. The mice injected with XJB-5-125, XJB-7-75, JP4-039 or acetylated-resveratrol had increased survival compared to control irradiated mice (p ≤ 0.0004). Therefore, four new small molecules have been identified which demonstrate significant radioprotective properties both in vitro and in vivo.

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