|Year : 2018 | Volume
| Issue : 2 | Page : 102-105
A systematic organization of bioinformatics database of radiosensitizers and radioprotectors
PM Dongre, Amruta Joshi
Department of Biophysics, University of Mumbai, Mumbai, Maharashtra, India
|Date of Web Publication||22-May-2018|
Dr. P M Dongre
Department of Biophysics, University of Mumbai, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
Radiosensitizers and radioprotectors are the compounds that modify the radiation therapy treatment. Radiosensitizers make tumor cell more sensitive to radiation therapy which increases the effectiveness of cancer treatment, whereas radioprotectors are the compounds that reduce the damage/spare normal tissue. Several of these compounds have been studied using appropriate biological model system and their efficacy is reported in literature. The main objectives of the bioinformatics database is to bring on single platform for researchers and clinicians. Therefore, we have developed bioinformatics database of radiosensitizers and radioprotectors using information available in PubMed, scientific journals, and other scientific sources. The collected information of these compounds systematically organized on single platform where a user can browse typical information of the compound. The information pertaining to these compounds is mainly on structural features, radiobiological aspects, biological targets, clinical trials, pharmacological aspects, toxicity, etc. Hence, the database would help clinicians, researchers, and scientists for the improvement of radiation therapy treatment.
Keywords: Biological targets, pharmacological aspects, radioprotectors, radiosensitizers
|How to cite this article:|
Dongre P M, Joshi A. A systematic organization of bioinformatics database of radiosensitizers and radioprotectors. J Radiat Cancer Res 2018;9:102-5
|How to cite this URL:|
Dongre P M, Joshi A. A systematic organization of bioinformatics database of radiosensitizers and radioprotectors. J Radiat Cancer Res [serial online] 2018 [cited 2018 Aug 21];9:102-5. Available from: http://www.journalrcr.org/text.asp?2018/9/2/102/232984
| Introduction|| |
Radiotherapy is regarded as one of the most important therapeutic modalities for the treatment of malignant lesions. This field is undergoing rapid advancements in the recent times. With the use of radiosensitizing and radioprotective agents, the course of radiotherapy has improved the sensitization of tumor cells and protection of normal cells, respectively.,
Radiosensitizers are the compounds that apparently act in different ways such as promoting fixation of the free radicals produced by radiation damage at the molecular level. The mechanism of action is similar to the oxygen effect, in which biochemical reactions in the damaged molecules prevent repair of the cellular radiation damage. Free radicals such as.OH are captured by the electron affinity of the radiosensitizers, rendering the molecules incapable of repair. Radioprotectors are compounds that are designed to reduce the damage in normal tissues caused by radiation. These compounds are often antioxidants and must be present before or at the time of radiation for effectiveness. Other agents, termed mitigators, may be used to minimize toxicity even after radiation has been delivered. This article tries to discuss the various aspects of radiosensitizers, radioprotectors, and radiation mitigators including the newer agents.
Radiosensitizers are intended to enhance tumor cell killing while having much less effect on normal tissues. Some drugs target different physiological characteristics of the tumor, particularly hypoxia associated with radioresistance. Oxygen is the definitive hypoxic cell radiosensitizer, the large differential radiosensitivity of oxic versus hypoxic cells being an attractive factor. The combination of nicotinamide to reduce acute hypoxia with normobaric carbogen breathing is showing clinical promise. “Electron-affinic” chemicals that react with DNA-free radicals have the potential for universal activity to combat hypoxia-associated radioresistance; a nitroimidazole, nimorazole, is clinically effective at tolerable doses. Hypoxia-specific cytotoxins, such as tirapazamine, are valuable adjuncts to radiotherapy. Nitric oxide is a potent hypoxic cell radiosensitizer, variations in endogenous levels might have prognostic significance, and routes to deliver nitric oxide specifically to tumors are being developed. In principle, many drugs can be delivered selectively to hypoxic tumors using either reductase enzymes or radiation-produced free radicals to activate drug release from electron-affinic prodrugs.,
A redox-active agent based on a gadolinium chelate is being evaluated clinically. Pyrimidines substituted with bromine or iodine are incorporated into DNA and enhance free radical damage; fluoropyrimidines act by different mechanisms. A wide variety of drugs that influence the nature or repair of DNA damage are being evaluated in conjunction with radiation; it is often difficult to define the mechanisms underlying chemoradiation regimens.
The aim of this report was to critically review and analyze the available compounds studied as radiosensitizers, radioprotectors, and radiation mitigators and make it users on a single platform for further investigation.
| Materials and Methods|| |
We used the electronic search for the keywords “radiosensitizers,” “radioprotectors,” “radiation mitigators” on PubMed for the inclusion of previously published articles and further search of reference papers on individual radiosensitizing and radioprotecting agents. All the information was collected from the above source and critically evaluated and categorized in different configurations such as general feature of compounds, biological targets of compounds, radiobiological aspects, biological models used, clinical study, pharmacological aspects, and toxicity of compound. A typical web portal (at copy write) is designed [Figure 1], [Figure 2], [Figure 3], [Figure 4] for the inclusion of these features where a user can electronically browse the particular information.
| Results and Discussion|| |
A total of 100 compounds have been critically evaluated based on appropriate information available on PubMed, various peer-reviewed research journals, books, etc. The information of these compounds categorized in different characteristics such as physicochemical properties, targets of these compounds, radiobiological study, clinical trials, toxicity, pharmacological aspects, and chemical intervention. For this purpose, a typical web portal is designed for the inclusion of these features [Figure 1], [Figure 2], [Figure 3], [Figure 4].
It is a simple and user-friendly browsing technique. To obtain information on these compounds, a user has to log in to the website (very soon, it will be activated). After logged in, a typical page will be displayed [Figure 1] with various icons such as Home, Introduction, Search, Institution, Help, and Contact. Its home page gives brief introduction of the program and its importance. Similarly, an alphabetical bar will show the initial letter of the compounds (e.g., A-actinomycin). The next step is that the users can hit/click any icon on the bar where new page will appear for particular information. For example, if user hits home icon, new page will be appear and it will display the brief introduction of database of radiomodifiers. If user clicks any alphabet or known compound, a particular page will be opened and that page will show the numbers of drugs/compounds under that alphabets. Then, user can click on any of the specified compounds for further browsing. The various features of particular compound will be displayed such as general features, biological targets, radiobiological study/aspects, toxicity study, clinical study, chemical intervention, and pharmacological aspects. [Figure 2], [Figure 3], [Figure 4]. Further, each aspect of particular compound can be browsed. For example, under general feature – the information of compound is on generic name, IUPAC name, structure, chemical nature, physicochemical properties, action and indications, etc.; under radiobiological aspects – the information is on radiation response to biological system, dose-modifying ability, LD50, etc.; under biological model – the information is pertaining to various models used in the study (membranes, animals, tissues, etc.); under biological targets – the information will be on various targets of the compounds such as DNA, membrane, proteins, and lipids; under pharmacological aspects – information is on half-life, drug availability, metabolism, excretion, etc.; under toxicity – information is on adverse reactions, mutagenicity, carcinogenicity, etc.; under clinical study – the information is on evaluation of the clinical study of compounds, patient risk, design of study, etc. This database also provides the information of the institutions who are actively involved in radiobiological research; however, it is not updated now, but in the future, it is going to be updated. Every feature of these compounds is linked (available) to the particular reference research paper, book, website, etc.
Thus, the direct link of these compounds will be available on the University of Mumbai web portal (www.mu.ac.in) as well as on the Department of Biophysics web portal. This comprehensive database will be useful for clinicians, researchers, and radiation workers. Along with this exhaustive exercise, we have invited feedback from the users for further improvement or revision of this bioinformatics database. Similarly, interested researcher and clinician can also upload his/her experimental data (peer reviewed).
We gratefully acknowledge the Board of Research and Nuclear Science, Department of Atomic Energy, Government of India, for financial support, grant no. 2009/37/BRNS/3303, dated 4.2.2010.
Financial support and sponsorship
Board of Research and Nuclear Sciences, Department of Atomic Energy, Govt. of India, Grant No: 2009/37/BRNS/3303, Dated- 4-2-2010.
Conflicts of interest
There are no conflicts of interest.
| References|| |
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Huilgol NG, Nair CK, Kagiya VT. Chlorpromazine – A hypoxic cell sensitizer a new role for an old drug in radiation a contemporary audit. New Delhi: Narosa Publication; 2001.
Bump EA, Malkar K. Radioprotectors, Chemical, Biological and Clinical Perspective. London: CRC Press, Taylor and Francis Group; 1997.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]