*Corresponding Author Address: .S.Bhagavathy, Research Scholar, Bharathiar University, Coimbatore, India ., E-mail :bhagavathy12@rediffmail.com World Journal of Pharmaceutical Sciences ISSN (Print): 2321-3310; ISSN (Online): 2321-3086 Published by Atom and Cell Publishers © All Rights Reserved Available online at: http://www.wjpsonline.org/ Original Article Molecular docking of retinoic acid with cytochrome P450 isoforms CYP1A1, 1A2 and 1B1 – a potential drug target against carcinogen benzo(a)pyrene S. Bhagavathy* 1 and P. Sumathi 2 1 Research Scholar, Bharathiar University, Coimbatore, Tamilnadu, India 2 Assiastant Professor, Department of Biochemistry, Queen Mary’s College, Chennai, Tamilnadu, India Received: 30-09-2014 / Revised: 04-11-2014 / Accepted: 12-11-2014 ABSTRACT Human cytochromes present in lungs, plays an important role in the metabolic activation of chemical carcinogens, and in particular, is thought to be linked to lung cancer. The mechanism of carcinogenesis is related to the enzyme's ability to oxidize highly toxic compounds, such as polycyclic aromatic hydrocarbons (PAHs), to their carcinogenic derivatives. In order to better understand Cytochrome P450 (CYP) function, a homology model of this enzyme has been constructed with its isoforms CYP 1A1, CYP 1A2, and CYP 1B1. CYP substrates, such as benzo[a]pyrene [B(a)P], benzo[a]pyrene 7,8 dihydrodiol [B(a)P diol] and Retinoic acid (RA) were docked into the active site of the model, binding interactions and key amino acid residues able to interact with the substrate, have been identified. The analysis of enzyme-substrate interactions indicated that Vander wails, hydrogen and hydrophobic interactions are mainly responsible for binding of these substrates in the active site. CYP 1A1 and 1A2 shows the binding similarities comparing with CYP1B1. Key residues Ala and Gly in the position 317 and 318 play an important role both in procarcinogen activation and RA binding. Additionally, the binding free energy calculations were performed for the three substrates. Lower binding energy required for RA binding than procarcinogen activation. The obtained values were similar to those observed experimentally, which suggests that this approach might be useful for prediction of binding constants. Key Words: Retinoic acid, Benzo(a)Pyrene, Benzo(a)Pyrene 7,8 dihydrodiol, Cytochrome P450 1A1, Cytochrome P450 1A2, Cytochrome P450 1B1. INTRODUCTION Carotenoids have been reported to have multiple biological activities such as anticarcinogic, antimutagenic, antioxidant, anti-inflammatory, antiproliferative and antiartherogenic properties and as a chemopreventive agent against cancer in various organs like lung, stomach, colon, breast and prostate. Also carotenoids can play important role in immune response, neoplastic transformation and control of growth and intracellular communication. The biological activities of carotenoids as β-carotene are related in general to their ability to form vitamin A in the body [1]. Carotenoids are considered potential membrane antioxidants due to the way they react with oxygen FR and singlet oxygen - a non radical pro oxidant found in biological system and capable of damaging protein, lipids and DNA [2]. Carotenoids strongly interact with ROS and thus act in plant and animal organisms as potent FR quenchers, singlet oxygen scavengers, lipid antioxidants and chain breaking antioxidants and some of them also serve as precursors for retinoids. Consequently carotenoids have been instantly studied by organic chemists, food chemists, biologists, physiologists, medical doctors and recently also by environmentalists and great demands have been placed on their identification and determination [3, 4]. The nutritional and therapeutic relevance of dietary carotenoids is attributed to their ability to act as provitamin A, they can be converted into vitamin A and vitamin A analogue by the human body. Moreover, vitamin A plays a protective role by preventing the formation of ROS [5]. In many animals, the most important metabolic product of carotenoids is the retinoids and the metabolic reactions of carotenoids in animals are essentially oxidative. However, pathways of reductive metabolism have been discovered and this has opened up the possibility that xanthophylls could be precursors of retinoids - retinol, 3- dehydroretinol and 3-dehydroretinal. From the