Spin labeled antioxidants protect bacteria against the toxicity of alkylating antitumor drug CCNU

Gadjeva, V.; Lazarova, G.; Zheleva, A.

doi:10.1016/s0378-4274(03)00234-0

Cited by 10 publications

(3 citation statements)

References 14 publications

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“…Activation also produces isocyanates that carbamoylate lysine residues damaging cellular proteins [78]. This drug showed moderate bactericidal activity against E. coli and S. aureus [79].…”

Section: Alkylating Agents and Dna Crosslinkersmentioning

confidence: 99%

Repurposing of Anticancer Drugs for the Treatment of Bacterial Infections

Soo

Kwan

Quezada

et al. 2017

CTMC

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Despite the fact that bacterial infections are one of the leading causes of death worldwide and that mortality rates are increasing at alarming rates, no new antibiotics have been produced by the pharmaceutical industry in more than a decade. The situation is so dire that the World Health Organization warned that we may enter a "post-antibiotic era" within this century; accordingly, bacteria resistant against all known antibiotics are becoming common and already producing untreatable infections. Although several novel approaches to combat bacterial infections have been proposed, they have yet to be implemented in clinical practice. Hence, we propose that a more plausible and faster approach is the utilization of drugs originally developed for other purposes besides antimicrobial activity. Among these are some anticancer molecules proven effective in vitro for eliminating recalcitrant, multidrug tolerant bacteria; some of which also protect animals from infections and recently are undergoing clinical trials. In this review, we highlight the similarities between cancer cells/tumors and bacterial infections, and present evidence that supports the utilization of some anticancer drugs, including 5-fluorouracil (5-FU), gallium (Ga) compounds, and mitomycin C, as antibacterials. Each of these drugs has some promising properties such as broad activity (all three compounds), dual antibiotic and antivirulence properties (5-FU), efficacy against multidrug resistant strains (Ga), and the ability to kill metabolically dormant persister cells which cause chronic infections (mitomycin C).

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“…Activation also produces isocyanates that carbamoylate lysine residues damaging cellular proteins [78]. This drug showed moderate bactericidal activity against E. coli and S. aureus [79].…”

Section: Alkylating Agents and Dna Crosslinkersmentioning

confidence: 99%

Repurposing of Anticancer Drugs for the Treatment of Bacterial Infections

Soo

Kwan

Quezada

et al. 2017

CTMC

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“…This finding encourages us to synthesize a number of spin-labeled analogues of the anticancer drug 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU). Some of these compounds showed advantages over CCNU, having lower toxicity and higher anticancer activity against some experimental tumor models [26, 27]. By EPR method, we have shown that spin-labeled nitrosoureas and their precursor 4-amino TMPO can scavenge • O 2 − and so exhibit high superoxide-scavenging activity (SSA) [28].…”

Section: Introductionmentioning

confidence: 99%

Protective Effect of Spin-Labeled 1-Ethyl-1-nitrosourea against Oxidative Stress in Liver Induced by Antitumor Drugs and Radiation

Gadjeva

Grigorov

Nikolova

et al. 2013

BioMed Research International

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This study was carried out to investigate possible protection effect of 1-ethyl-3-[4-(2,2,6,6-tetramethylpiperidine-1-oxyl)]-1-nitrosourea (SLENU), synthesized in our laboratory, against oxidative liver injuries induced in mice treated by antitumor drugs: doxorubicin (DOX), bleomycin (BLM), or gamma irradiation (R). Specifically, alterations in some biomarkers of oxidative stress, such as lipid peroxidation products measured as malondialdehyde (MDA) levels and activities of the antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT), were studied in liver homogenates isolated from tumor bearing C57 black mice after i.p. treatment with solutions of DOX (60 mg/kg), BLM (60 mg/kg), or after total body gamma-irradiation with a single dose of 5 Gy. The same biomarkers were also measured after i.p. pretreatment of mice with SLENU (100 mg/kg). Statistical significant increased MDA levels and SOD and CAT enzymes activities were found in the liver homogenates of tumor bearing mice after alone treatment with DOX or gamma-irradiation compared to the control mice, while these parameters were insignificantly increased after BLM administration compared to the same controls.

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“…Following this finding, we have synthesised a number of spin-labelled analogues of the anticancer drug 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU). Some of these compounds showed advantages over CCNU, by having lower toxicity and higher anticancer activity against some experimental tumour models [11]- [14]. Using the EPR method we had shown that spin-labelled nitrosoureas could scavenge 2 O − ⋅ and thus exhibited high superoxide scavenging activity (SSA) [15].…”

Section: Introductionmentioning

confidence: 99%

Spin-Labelled 1-Ethyl-1-Nitrosourea Prevents Doxorubicin and Bleomycin-Induced Oxidative Stress in Lungs, Hearts and Kidneys of Tumour-Bearing Mice

Gadjeva¹,

Nikolova²,

Grigorov³

et al. 2014

ABC

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This study was carried out to determine the possible protective effect of 1-ethyl-3-[4-(2, 2, 6, 6-tetramethylpiperidine-1-oxyl)]-1-nitrosourea (SLENU), recently synthesised in our laboratory on doxorubicin and bleomycin-induced oxidative toxicity in C57 black tumour-bearing mice. Specifically, alterations in some biomarkers of oxidative stress, such as lipid peroxidation products measured as malondialdehyde (MDA) levels and activities of the antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT), were studied in lung, heart and kidney homogenates isolated from C57 black tumor-bearing mice after i.p. treatment with solutions of DOX (60 mg/kg) and BLM (60 mg/kg). The same biomarkers were also measured after i.p. pretreatment of mice with SLENU (100 mg/kg). After treatment with doxorubicin, heart and kidney homogenates of mice had significantly higher productions of lipid peroxidation compared to lung homogenates. It was accompanied by increased activity of the antioxidant defence enzyme superoxide dismutase and decreased activity of catalase. Bleomycin-induced oxidative stress was confirmed by significantly higher production of lipid peroxidation in lungs compared to heart homogenates, elevation of the antioxidant activity of superoxide dismutase and decreased activity of catalase enzymes. After pretreatment of the mice with SLENU, the levels of all studied oxidative stress biomarkers were significantly improved

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Spin labeled antioxidants protect bacteria against the toxicity of alkylating antitumor drug CCNU

Cited by 10 publications

References 14 publications

Repurposing of Anticancer Drugs for the Treatment of Bacterial Infections

Repurposing of Anticancer Drugs for the Treatment of Bacterial Infections

Protective Effect of Spin-Labeled 1-Ethyl-1-nitrosourea against Oxidative Stress in Liver Induced by Antitumor Drugs and Radiation

Spin-Labelled 1-Ethyl-1-Nitrosourea Prevents Doxorubicin and Bleomycin-Induced Oxidative Stress in Lungs, Hearts and Kidneys of Tumour-Bearing Mice

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