Sasikala Maadwar et al. Int. Res. J. Pharm. 2019, 10 (4) 190 INTERNATIONAL RESEARCH JOURNAL OF PHARMACY www.irjponline.com ISSN 2230 – 8407 Research Article EFFICIENT SYNTHESIS AND CYTOTOXIC SCREENING OF 3,3 DISUBSTITUTED OXINDOLE DERIVATIVES Sasikala Maadwar 1,2 *, Rajitha Galla 1 , Santhosh K. G 1,2 1 Institute of Pharmaceutical Technology, Sri Padmavati Mahila Visvavidyalayam, Tirupati, India 2 Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology, Hyderabad, India *Corresponding Author Email: maadwarsasikala@gmail.com Article Received on: 13/02/19 Approved for publication: 02/04/19 DOI: 10.7897/2230-8407.1004148 ABSTRACT 3,3-disubstituted oxindole derivatives were synthesised by treating isatins with electron rich benzene derivatives at room temperature by using BF3O(Et)2 as catalyst which reduced the synthesis time. The compounds were evaluated for cytotoxic activity against human breast cancer cells (MCF7) and human ovarian carcinoma cells (SKVO3) by using MTT assay. Compounds 1(7.2±0.22μM and 11.80.21±μM), 2(7.10.24±μM and 9.8±0.27μM), exhibited relatively higher cytotoxic activity against both MCF7 and SKVO3 cell lines, respectively. Keywords: Isatins, Methoxy Benzenes, Boron Trifluoride Diethyl Etherate, MCF7 and SKVO3 INTRODUCTION Cancer is characterised by a change in controlled mechanisms that manage cell proliferation, differentiation and is continuing to be a major health problem in developing as well as undeveloped countries. Malignancy is caused by abnormalities in cells, which might be due to inherited genes or caused by exogenous agents including chemicals, radiation and some infectious agents 1 . Organic compounds with an oxindole framework are represented in a large family of a pharmaceutically active compounds and bioactive natural products. Particularly, spirooxindole and 3, 3- disubstituted derivatives were present in a number of alkaloids which possess significant biological activities. Such as anticancer 2 , antidepressant 3 , anticonvulsant 4 , antifungal 5 , anti- HIV 6 , anti-inflammatory 7 . During past decades, researchers have embarked on the development of new oxindole based anticancer agents 8-10 . 5-fluoro-3-substituted-2-oxoindole derivative compound SU11248 [Sutent] received FDA approval for the treatment of gastrointestinal stromal tumors and advanced renal cell carcinoma 11 . Due to the importance of oxindole motifs, several methods have been developed for the construction such structural motifs 12-19 . Despite of effectiveness, these methods involve use of expensive catalysts 20-22 , long reaction time 16,17,19,23 , tedious work up, vigorous reaction conditions 15 and poor yield 19 . Therefore there is need to develop efficient, convenient and practical protocol to synthesize oxindole scaffolds. In the present investigation, we have developed a rapid and efficient method for synthesis of methoxy benzene substituted oxindoles using boron trifluoride diethyl etherate as catalyst. The newly synthesized 3,3-disubstited oxindole are evaluated for their cytotoxic potentials against wild type human breast cancer cell line (MCF7) and human ovarian carcinoma cells (SKVO3). MATERIALS AND METHODS Chemistry All the starting materials procured from Sigma Aldrich and used without further purification. Solvents were of analytical grade. All the reactions were carried out with the use of standard techniques and were monitored by analytical TLC performed on pre-coated silica. General procedure for synthesis of 3,3-disubstituted oxindoles To 1.0 equivalent of isatin 1.5 equivalent of tri and di methoxy benzene was added in DCM in a RBF, stirred it for 2min, 0.2ml of [BF3O(Et)2] was added and stirred it for another 5-10 min (Scheme 1). Reaction was monitored by TLC, excess of reagent was quenched with solid sodium bicarbonate and directly loaded on to column. The structure of the compounds were confirmed by 1 H NMR, 13 CNMR, IR and Mass-spectroscopy. Elemental analysis: Calculated: C, 70.71; H,5.34; N,8.25, Found : C,70.72; H,5.31; N,8.27 5-chloro-3,3-bis(2,4,6-trimethoxyphenyl)indolin-2-one (1): Light red solid; Mp 180-182 o C; 1 H NMR (300 MHz, CDCl3): d 3.54 (s, 3H), 3.68 (s, 3H), 6.72 (s, 3H), 3.80 (s, 3H), 3.85 (s, 3H), 3.88 (s, 3H), 5.14 (s, 1H), 6.09 (dd, J = 2.13 Hz and 8.39 Hz, 1H), 6.20 (dd, J = 2.13 Hz and 5.95 Hz, 2H), 6.22 (d, J = 2.28 Hz, 1H), 6.74 (s, 1H), 7.00 (s, 1H), 8.68 (br s, 1H) ppm. 13 CNMR (75 MHz, CDCl3): d42.5, 55.2, 55.3, 55.7, 55.9, 89.6, 89.8 90.6, 90.8, 91.6, 105.7, 108.7, 109.9, 113.2, 124.3, 127.1, 128.0, 131.0, 132.3, 139.8, 158.2, 158.3, 158.8, 159.3, 161.0, 180.1 ppm.IR (KBr): ν = 809, 1116, 1153, 1225, 1458, 1609, 1707, 2936 cm -1 . MS-ESI: m/z = 500 [M+H] + , 522 [M+Na] + . Elemental analysis: Calculated: C,62.46; H,5.24; Cl,7.09; O,22.40, Found : C,62.44; H,5.23; Cl,7.08; O,22.40.