921 J. Indian Chem. Soc., Vol. 92, June 2015, pp. 921-924 Synthesis and study the anti-proliferative effect of new series of 1H-imidazo[4,5-c]quinoline derivatives in MCF-7 (human breast cancer) cells Natarajan Senthilkumar and Yesudass Dominic Ravichandran* Organic Chemistry Division, School of Advanced Sciences, VIT University, Vellore-632 014, Tamilnadu, India E-mail : dominic.y@vit.ac.in Abstract : New series of 2-(4-(7-fluoro-8-aryl-1H-imidazo[4,5-c]quinolin-1-yl)phenyl)acetonitrile derivatives of biological interest have been synthesized from commercially available 2-amino-5-bromo-4-fluorobenzoicacid with good yield (70%). Compounds 2-(4-(7-fluoro-8-phenyl-1 H-imidazo[4,5- c ]quinolin-1-yl)phenyl)acetonitrile (7a) and 2-(4-(7-fluoro-8-(4- iodophenyl)-1H-imidazo[4,5-c]quinolin-1-yl)phenyl)acetonitrile (7b) were also screened for anti-proliferative effect on MCF- 7 (human breast cancer cell line). Among them compound 7a showed moderate inhibition compared to control. Keywords : 1H-Imidazo[4,5-c]quinoline, 2-amino-5-bromo-4-fluorobenzoicacid, MCF-7, anti-proliferation assay. Introduction Breast cancer is the most prevalent form of cancer in women world over. MCF-7 cells are useful for in vitro breast cancer studies because the cell line has retained several ideal characteristics particular to the mammary epithelium. These include the ability for MCF-7 cells to process estrogens, in the form of estuarial, via estrogens receptors in the cell cytoplasm. This makes the MCF-7 cell line an estrogens receptor (ER) positive control cell line. In breast cancer cells containing oestrogen receptors both oestrogens and growth factors can stimulate prolif- eration, invasion and the secretion of a number of pro- teins. In the drug discovery activities, imidazo[4,5-c]- quinoline derivatives can be considered a privileged ATP- site-directed kinase lead structure and also were found to act as inhibitors of the PI3K/PKB-pathway 1 , selective dipeptidyl peptidase IV (DPP-4) 2 and TNF- (tumor ne- crosis factor-) suppressor 3 . Even though 1H-imidazo- [4,5,c]quinoline derivatives acted as a protein kinase in- hibitor 4 , in order to increase the rate of inhibition, fluo- rine was introduced in 7-position. Fluorine, being the second smallest substituent that meets the steric require- ments at enzyme receptor sites, the presence of fluorine increased lipid solubility and thereby improved the phar- macological activity. This may be due to the enhance- ment of the rate of absorption and transport of drugs in vivo and the aided hydrophobic interaction between drugs and binding sites on receptor or enzyme 5 . Furthermore, bromine was replaced by electron donating aryl group at 8-position of 1H-imidazo[4,5,c]quinoline to study the tox- icity of MCF-7 cells. Experimental 5-Bromo-4-fluoro-2-(2-nitrovinylamino)benzoic acid (1) : 1 H NMR (300 MHz, DMSO-d 6 ) :  13.0 (1H, d), 8.20 (1H, d), 8.0 (1H, m), 7.95 (1H, d), 6.90 (1H, d); LCMS (M-1) 304. 6-Bromo-7-fluoro-3-nitroquinolin-4-ol (2) : 1 H NMR (300 MHz, DMSO-d 6 ) :  13.1 (1H, br s), 9.25 (1H, s), 8.41 (1H, d), 7.61 (1H, d); LCMS (M+1) 286.6. 6-Bromo-4-chloro-7-fluoro-3-nitroquinoline (3) : 1 H NMR (300 MHz, DMSO-d 6 ) :  9.42 (1H, s), 8.76 (1H, d), 8.22 (1H, d); LCMS (M+1) 304.9. 2-(4-(6-Bromo-7-fluoro-3-nitroquinolin-4- ylamino)phenyl)acetonitrile (4) : 1 H NMR (300 MHz, DMSO-d 6 ) :  10.15 (1H, br s), 9.05 (1H, s), 8.95 (1H, d), 7.95 (1H, d), 7.3 (1H, d), 7.1 (1H, d), 4.05 (1H, s); LCMS (M+1) 400.8. 2-(4-(3-Amino-6-bromo-7-fluoroquinolin-4-ylamino)- phenyl)acetonitrile (5) : 1 H NMR (300 MHz, DMSO-d 6 ) :  8.64 (1H, s), 8.05 (2H, m), 7.76 (1H, d), 7.1 (1H, d), 6.52 (1H, d), 5.42 (2H, br s), 3.84 (1H, s); LCMS (M+1) 370.9.