Synthesis and radioprotective effects of novel benzyl naphthyl sulfoxide (sulfone) derivatives transformed from Ex-RAD

Tang, Lin; Peng, Tao; Wang, Gang; Wen, Xiang; Sun, Yujing; Zhang, Shouguo; Liu, Shuchen; Wang, Lin

doi:10.1039/c7md00573c

Cited by 14 publications

(8 citation statements)

References 14 publications

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“…Additional 'small molecule' protectants related to benzyl naphthyl sulfoxide derivatives have been designed and synthesized as well. One of the derivatives demonstrated radioprotective efficacy when tested in acutely irradiated mice and was assessed using 'survival' as the endpoint (Tang et al 2018).…”

Section: Chlorobenzylsulfonesmentioning

confidence: 99%

Radiation countermeasures for hematopoietic acute radiation syndrome: growth factors, cytokines and beyond

Singh

Seed²

2021

International Journal of Radiation Biology

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Purpose: The intent of this article is to report the status of some of the pharmaceuticals currently in late stage development for possible use for individuals unwantedly and acutely injured as a result of radiological/nuclear exposures. The two major questions we attempt to address here are: (a) What medicinals are currently deemed by regulatory authorities (US FDA) to be safe and effective and are being stockpiled? (b) What additional agents might be needed to make the federal/ state/local medicinal repositories more robust and useful in effectively managing contingencies involving radiation overexposures? Conclusions: A limited number (precisely four) of medicinals have been deemed safe and effective, and are approved by the US FDA for the 'hematopoietic acute radiation syndrome (H-ARS).' These agents are largely recombinant growth factors (e.g. rhuG-CSF/filgrastim, rhuGM-CSF/sargramostim) that target and stimulate myeloid progenitors within bone marrow. Romiplostim, a small molecular agonist that enhances platelet production via stimulation of bone marrow megakaryocytes, has been recently approved and indicated for H-ARS. It is critical that additional agents for other major sub-syndromes of ARS (gastrointestinal-ARS) be approved. Future success in developing such medicinals will undoubtedly entail some form of a polypharmaceutical strategy, or perhaps novel, bioengineered chimeric agents with multiple, radioprotective/radiomitigative functionalities.

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Section: Chlorobenzylsulfonesmentioning

confidence: 99%

Radiation countermeasures for hematopoietic acute radiation syndrome: growth factors, cytokines and beyond

Singh

Seed²

2021

International Journal of Radiation Biology

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“…With the increasing use of nuclear technology, the potential risk of radiation exposure is becoming a big cause of concern 1 . People are prone to ionizing radiation (IR) exposure during terror attacks, nuclear accidents, space exploration and radiotherapy 2‐4 . IR could cause destructive effect on normal cells in two ways: radiation energy acts directly on biological macromolecules and leads to ionisation or excitation of macromolecules, this is the direct effect of IR; rays act on water molecules and accelerate the generation of reactive oxygen species (ROS), which may attack the surrounding macromolecules, this is the indirect effect of IR 5 .…”

Section: Introductionmentioning

confidence: 99%

“…To date, numerous natural products and synthetic compounds have been evaluated for their potential as effective radioprotectors 3,15 . Among these, amifostine is the only radioprotective agent approved by the Food and Drug Administration (FDA) for decreasing adverse reactions in patients undergoing radiation therapy 4 . However, amifostine can only be administrated intravenously and has been shown to have multiple adverse effects, such as nausea, hypotension, cephalalgia, fainting and transient hypocalcemia 4,5,13 .…”

Section: Introductionmentioning

confidence: 99%

“…Among these, amifostine is the only radioprotective agent approved by the Food and Drug Administration (FDA) for decreasing adverse reactions in patients undergoing radiation therapy 4 . However, amifostine can only be administrated intravenously and has been shown to have multiple adverse effects, such as nausea, hypotension, cephalalgia, fainting and transient hypocalcemia 4,5,13 . Hence, there is an urgent need to develop efficient, convenient and less toxic radioprotectors to protect normal human tissues from radiation damage.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and radioprotective effects of novel hybrid compounds containing edaravone analogue and 3‐n‐butylphthalide ring‐opening derivatives

Wang

Miao

et al. 2021

J Cellular Molecular Medi

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As the potential risk of radiation exposure is increasing, radioprotectors studies are gaining importance. In this study, novel hybrid compounds containing edaravone analogue and 3‐n‐butylphthalide ring‐opening derivatives were synthesized, and their radioprotective effects were evaluated. Among these, compound 10a displayed the highest radioprotective activity in IEC‐6 and HFL‐1 cells. Its oral administration increased the survival rates of irradiated mice and alleviated total body irradiation (TBI)‐induced hematopoietic damage by mitigating myelosuppression and improving hematopoietic stem/progenitor cell frequencies. Furthermore, 10a treatment prevented abdominal irradiation (ABI)‐induced structural damage to the small intestine. Experiment results demonstrated that 10a increased the number of Lgr5+ intestinal stem cells, lysozyme+ Paneth cells and Ki67+ transient amplifying cells, and reduced apoptosis of the intestinal epithelium cells in irradiated mice. Moreover, in vitro and in vivo studies demonstrated that the radioprotective activity of 10a is associated to the reduction of oxidative stress and the inhibition of DNA damage. Furthermore, compound 10a downregulated the expressions of p53, Bax, caspase‐9 and caspase‐3, and upregulated the expression of Bcl‐2, suggesting that it could prevent irradiation‐induced intestinal damage through the p53‐dependent apoptotic pathway. Collectively, these findings demonstrate that 10a is beneficial for the prevention of radiation damage and has the potential to be a radioprotector.

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“…Humans may be exposed to ionizing radiation (IR) during radiological attacks and accidents, exploration of the universe, and radiation therapy [1][2][3]. Under these cases, IR can cause damage to macromolecules in cells through two mechanisms: direct action, in which direct deposition of radiant energy on biological molecules cause their ionization or excitation, or the indirect action, in which radiant energy acts on water molecules and produces reactive oxygen species (ROS), which can disrupt the structure of biomolecules [4].…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of a Novel Aminothiol Compound as Potential Radioprotector

Wang

Miao

et al. 2021

Oxidative Medicine and Cellular Longevity

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The risk of radiation damage has increased with the rapid development of nuclear technology and radiotherapy. Hence, research on radioprotective agents is of utmost importance. In the present study, a novel aminothiol compound 12, containing a linear alkylamino backbone and three terminal thiols, was synthesized. Owing to the appropriate capped groups in the chains, it has an improved permeability and oral bioavailability compared to other radioprotective agents. Oral administration of compound 12 improved the survival of mice that received lethal doses of γ-irradiation. Experimental results demonstrated that compound 12 not only mitigated total body irradiation-induced hematopoietic injury by increasing the frequencies of hematopoietic stem and progenitor cells but also prevented abdominal irradiation-induced intestinal injury by increasing the survival of Lgr5+ intestinal cells, lysozyme+ Paneth cells, and Ki67+ cells. In addition, compound 12 decreased oxidative stress by upregulating the expression of Nrf2 and NQO1 and downregulating the expression of NOX1. Further, compound 12 inhibited γ-irradiation-induced DNA damage and alleviated G2/M phase arrest. Moreover, compound 12 decreased the levels of p53 and Bax and increased the level of Bcl-2, demonstrating that it may suppress radiation-induced apoptosis via the p53 pathway. These results indicate that compound 12 has the possibility of preventing radiation injury and can be a potential radioprotector for clinical applications.

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Synthesis and radioprotective effects of novel benzyl naphthyl sulfoxide (sulfone) derivatives transformed from Ex-RAD

Cited by 14 publications

References 14 publications

Radiation countermeasures for hematopoietic acute radiation syndrome: growth factors, cytokines and beyond

Radiation countermeasures for hematopoietic acute radiation syndrome: growth factors, cytokines and beyond

Synthesis and radioprotective effects of novel hybrid compounds containing edaravone analogue and 3‐n‐butylphthalide ring‐opening derivatives

Design, Synthesis, and Biological Evaluation of a Novel Aminothiol Compound as Potential Radioprotector

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