Design, Synthesis, Characterization and Pharmacological Evaluation of mTOR Inhibitors for Anticancer Activity.

Cancer can be defined as a disease in which a group of abnormal cells grow uncontrollably by disregarding the normal rules of cell division. Cancers arise approximately in one among every three individuals. DNA mutations arise normally at a frequency of 1 in every 20 million per gene per cell division. The average number of cells formed in any individual during an average lifetime is 1016 (10 million cells being replaced every second!). Risk of cancers are increased by infectious agents including viruses [Hepatitis B virus (HBV1), Human Papillomavirus (HPV), Human Immunodeficiency Virus(HIV)-increase risk of Nasopharyngeal, Cervical carcinomas and Kaposi’s Sarcoma] and bacteria such as Helicobacter pylori (Stomach cancers). Candidate molecules were docked for anticancer activity against the modeled protein target mTOR using drug design software (Maestro 9.1). Twenty five scaffolds were screened with high docking score against mTOR inhibitor. These compounds also passed Lipinski’s rule. The scaffold containing quinoline nucleus was selected on the basis of synthetic feasibility. All the synthesized compounds were characterized by UV spectroscopy, IR spectroscopy, NMR spectroscopy and MASS spectrometry and reported as pure. All the synthesized compounds were subjected to acute toxicity studies to fix the LD50. The LD50 value of the title compounds (C1-C5) was expected to be in category 4 i.e. > 300-2000mg/kg body weight. All the synthesized compounds were subjected to invitro experiment to determine anticancer activity using MTT assay procedure against mTOR inhibitor and found to be effective