Cancer

Journal of Molecular Structure (Theochem) 640 (2003) 163–165 www.elsevier.com/locate/theochem

Cancer protector activity of antioxidant compounds
˜ ˜ M.B.C. Leaoa,*, F. Neri de Souzaa, C.A. Taftb, A.C. Pavaoa
b

´ Departamento de Quımica Fundamental, Universidade Federal de Pernambuco, 50960-910 Recife, PE, Brazil ´ Centro Brasileiro de Pesquisas Fısicas—CBPF/MCT, Rua Dr. Xavier Sigaud,150-Urca, 22290-180, Urca, Rio de Janeiro, Brazil Received 25 March 2003; accepted 22 August 2003

a

Abstract Considering a DNA to carcinogen electron transfer mechanism for the carcinogenesis process whereas carcinogens react as a electrophilic and DNA as nucleophilic species we propose that the cancer protecting compounds will compete with the DNA for the donation of the electron for thecarcinogens. In this work, theoretical calculations of several compounds with well-known protecting activity are performed. The results were treated by a multivariant analysis (principal component analysis) in order to relate the calculated electronic parameters with the protecting activities. q 2003 Elsevier B.V. All rights reserved.
Keywords: Carcinogen; Antioxidant; DNA

1. Introduction Cancer isthe largest cause of death for both men and women, claiming worldwide over 6 million lives each year. The American Academy of Nutritional Research informs that that there is enough knowledge in the medical literature that supports the theory that antioxidants have a protecting effect against cancer. These substances should offer protection against premature aging, as well as chronic anddegenerative diseases. In general, the antioxidants that receive more attention among the researchers are vitamins E, C and Beta-carotene [1 –5]. Many studies indicate an inverse relationship between the individual that takes antioxidant regularly, (measured by the type of food and alimentary
* Corresponding author. ˜ E-mail address: taft@cbpf.br (M.B.C. Leao). 0166-1280/$ - see front matter q 2003Elsevier B.V. All rights reserved. doi:10.1016/j.theochem.2003.08.135

supplements, or through the level of antioxidants found in the blood), and the occurrence of different types of cancer. Damages caused by free radicals on cells affect the DNA molecule such that, depending on the severity of these effects, the DNA may be altered and create an abnormal cell that has the potential to continuereproduction until cancer is developed. Therapies with supplements of antioxidants can protect the body against damaged DNA yielding protection against free radicals [1 –6]. Various mechanisms of protection by antioxidants have been identified. First, it was shown that the antioxidants support and increase the effectiveness of the immunologic system of the body during combat of the abnormal cells(tumors). The antioxidants protect the body against the cancer fighting against the harmful effects of the free radicals The antioxidant resveratrol due to its inhibitory action on ciclooxigenase (COX), responsible for the catalysis and

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conversion of the araquidonic acid and the consequent possibility todevelop cancerous cells, should indicate a good protecting activity [1 – 6]. We note that the antioxidants also protect the body against the possibility of developing cancer due to the direct interaction with a wide range of chemical substances in the atmosphere considered carcinogenic. In this paper, we have analysed the protective action of the antioxidants resveratrol (3,5,40-trihydroxy-trans-stilbene) and ascorbic acid in comparison with some anti-inflammatory medicaments such as aspirin, sulindac and indomethacin.

2. A DNA – carcinogen interaction model The protecting substances should act in competition with the DNA (guanine) for the donation of the electron to the carcinogen, as described in Fig. 1. As compared to the DNA these protecting drugs should be able to more easily donate...