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Synthesis, characterization and in vitro anti-tumor activities of novel 9-ethyl-9H-purine derivatives

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Newer series of 9-ethyl-9H-purine derivatives (EPD) were synthesized and screened for their efficacy in inhibiting the proliferation of various tumor cells in vitro. We evaluated the effects of EPD against HeLa, SiHa, CaSki (human cervical cancer cells), LM8, LM8G7 (murine osteosarcoma cells), OVSAHO and SKOV-3 (human ovarian cancer cells). The chemical structures of the EPD were confirmed by 1H NMR and LCMS analyses. The inhibitory effects of EPD were studied by using trypan blue exclusion, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and TetraColor One reagents. Furthermore, SAR studies revealed that the presence of trifluoromethoxy and trifluromethyl group in 4b and 4g, respectively are responsible for the significant activity of the EPD against cervical cancer cells and the presence of isopropoxy group in 4f has influence in inhibiting the proliferation of osteosarcoma and ovarian cancer cell types.

Scheme for the synthesis of 9-ethyl-9H-purine

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This work was supported by World Bank under Technical Education Quality Improvement Programme (TEQUIP). SNS thank Prof. Sudhir Krishna, National Center for Biological Sciences (NCBS) for help related to biological studies. Basappa thanks Prof. K. Sugahara (Hokkaido University, JAPAN) for providing the facility and JSPS for the post doctoral fellowship. Amit G acknowledges NCBS (TIFR) for postdoctoral fellowship. SNS express his sincere gratitude to JSS Mahavidyapeetha and Dr. B.G. Sangameshwara for the encouragement towards this research work. We gratefully acknowledge Dr. Pooja Grover, Dr. Kavitha and Dr. Vinaya for critically reading the manuscript.

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Correspondence to Kanchugarakoppal S. Rangappa, B. S. Priya or S. Nanjunda Swamy.

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Raghu Ningegowda and Amit Grover contributed equally to the work.

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Ningegowda, R., Grover, A., Basappa et al. Synthesis, characterization and in vitro anti-tumor activities of novel 9-ethyl-9H-purine derivatives. Invest New Drugs 28, 754–765 (2010).

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