IOSR Journal of Pharmacy and Biological Sciences (IOSR-JPBS) e-ISSN:2278-3008, p-ISSN:2319-7676. Volume 12, Issue 1 Ver. III (Jan. - Feb.2017), PP 01-04 www.iosrjournals.org DOI: 10.9790/3008-1201030104 www.iosrjournals.org 1 | Page Development of Nimbolide from Seeds of Azadirachta Indica Extract Assisted by Molecular Docking to Cyclin E, against Cervical Cancer Tribhuvan Singh 1 *, Harvinder Singh Saini 2 , S.V. Ranganayakulu 2 , S. Ravi 3 , K. Sudhakar 3 . 1 *Guru Nanak Institutions Technical Campus - School of Pharmacy Ibrahimpatnam, Hyderabad-501506 2 Guru Nanak Institutions Technical Campus - School of Engineering and Technology Ibrahimpatnam, Hyderabad-501506 3 Rural Development Society, R&D Center, Punjagutta, Hyderabad-500082 Abstract: The recent studies on Nimbolide, a robust cervical anticancer agent was identified for the separation of Nimbolide from Azadirachta indica berry collected from Ranga Reddy- Dist, the seeds were initially isolated, dried and transformed into coarse powder. The seed core was defatted and concentrated using methanol in a soxhlet apparatus. The methanolic extract obtained from seeds is subjected to High Performance Liquid Chromatography [HPLC] by direct reverse phase method for isolation of Nimbolide using Molecular Docking of Nimbolide through Molecular Operatin Environment [MOE] 2008 software. This declared that Nimbolide has capability of binding 12.3% to a Glycine 131 undergoing polar interactions. Nimbolide was found to interact with Cyclin E, was redeemed from the Protein Data Bank [PDB code; 1W98]. It was observed that Nimbolide showed an satisfactory increased life span (54.32 and 65.16), decreased the viable cells (52.3±1.5 and 32.5±1.3), and tumor volume (3.2±0.03 and 2.4±0.04). Keywords: Azadirachta Indica, Cervical Cancer, 5-Fluorouracil, (HeLa) Henrietta Lacks cell line, Molecular Docking, Nimbolide. I. Introduction The Cervical Cancer is defined as repetitive growth of the tumor at cervical region, the micro invasion of greater than 3 millimeter intensity of stomach to get spread up by metastasis less than 7 millimeter, that prolongs through pelvic sidewall up to the uterus and then further extends into lower third of the vagina. Chemotherapy is a frequently used therapy for cervical cancer medication, in which drugs like 5- fluorouracil, carboplatin, cisplatin, paclitaxel, topotecan, cyclophosphamide, gemcitabine, irinitecan, docetaxel, doxorubicin and mitomycin are used. All the above mentioned drugs have certain toxic side effects. Thus it is necessary for development of natural and safe anticancer agent for the treatment of cervical cancer. In this perspective some phytochemical constituents were distinguished, such as taxol, and vincristine [1] . There is increasing number of publications on Azadirachta indica and its extract to fight against cervical cancer. Azadirachta indica is evergreen, tropical, possessing oblique shaped green leaves and trunk of timber with insect repellent properties [2] . Roughly speaking, Azadirachta indica showed an anticancer activity by promoting the antioxidant enzyme, and modifying the intracellular components essential for cancer growth and development; such as Cyclin D, Cyclin B, Cyclin B1, Cyclin1, Cyclin E, P53, PCNA, P21,GST-P. Nimbolide was found to interact with the cell cycle kinetics in cancer cells by promoting the cell cycle arrest at G1/S or G2/M phase through suppression of Cyclin, CDKs and PCNA [3, 4, 5, 6] . Nimbolide can be extracted from Azadirachta indica kernel powder by using an organic solvent such as ethyl acetate for microwave-assisted extraction, and it is refluxed for 15 hrs. 100 grams of Azadirachta indica kernel powder gives near about 1gm of Nimbolide. The Study of Molecular docking was performed and gave a vision to the interacting mode of Nimbolide by using The Molecular Operating Environment (MOE) 2008 software. Recent studies discovered that Nimbolide has capability of binding 12.3% to a Glycine 131 with polar interactions. Nimbolide was known to combine with Cyclin E, which causes phosphorylation of cancer cell and stop the G1/S phase protein expression [7] . II. Materials And Methods 2.1 From Azadirachta indica Seeds Extraction of Nimbolide Nimbolide is an enhanced concentrate enclosing 60% active ingredient. The Azadirachta indica berries were obtained from local area then kernels were isolated from fruits. The seeds were dried and made in to coarse powder. The Azadirachta indica kernels were defatted using an organic solvent such as ethyl acetic acid in a dissolvable microwave (Make: Samsung, Model: 2015) by the extraction procedure. By using soxhlet