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Design, Synthesis and in vitro Cytotoxicity Evaluation of New Fluorinated Ionic Salt (S)-(+)-2,3-Dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11(10H,11aH)-dione as Strategies for Improving Anticonvulsant Activity
Corresponding Author(s) : V. Natchimuthu
Asian Journal of Chemistry,
Vol. 32 No. 4 (2020): Vol 32 Issue 4, 2020
Abstract
The reaction of (S)-(+)-2,3-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11(10H,11aH)-dione (1) with 4-(trifluoromethyl)benzoic acid (2, C8H5F3O2) in dimethylformamide leads to the formation of C8H5F3O2 (1) as a classical ionic salt 3. The structure of new compound has been characterized by FTIR, 1H NMR, 13C NMR, HRMS spectroscopy. The new compound was tested for in vitro cytotoxicity evaluation by MTT assay against breast adenocarcinoma cell line of MCF-7 cells. A new compound 3 (IC50:199 μM) emerged as minimal toxic when compared to clinical drugs carbamazepine, topiramate and benzodiazepine. A preliminary study of structure activity relationship revealed that the incorporation of fluoro or trifluoromethyl moiety into the compound, even through ionic bond formation, had a great effect on the biological activity and with less toxicity or side effects.
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- R.B. Aird, R.L. Masland and D.M. Woodbury, Epilepsy Res., 3, 77 (1989); https://doi.org/10.1016/0920-1211(89)90071-5
- J.O. McNamara, Nature, 399, A15 (1999); https://doi.org/10.1038/399a015
- R. Fisher, W.V.E. Boas, W. Blume, C. Elger, P. Genton, P. Lee and J. Engel, Epilepsia, 46, 470 (2005); https://doi.org/10.1111/j.0013-9580.2005.66104.x
- T.K. Banerjee, B.K. Ray, S.K. Das, A. Hazra, M.K. Ghosal, T. Roy, A. Chaudhuri and D.K. Raut, Epilepsia, 51, 2384 (2010); https://doi.org/10.1111/j.1528-1167.2010.02740.x
- S.I. Johannessen and C. Johannessen, Curr. Neuropharmacol., 8, 254 (2010); https://doi.org/10.2174/157015910792246254
- S.M. Sisodiya, W.R. Lin, B.N. Harding, M.V. Squier and M. Thom, Brain, 125, 22 (2002); https://doi.org/10.1093/brain/awf002
- A. Navale, S. Pawar, M. Deodhar and A. Kale, Med. Chem. Res., 22, 4316 (2013); https://doi.org/10.1007/s00044-012-0434-y
- G. Kramer, Epilepsia, 42, 55 (2001); https://doi.org/10.1046/j.1528-1157.2001.042suppl.3055.x
- P. Kwan and M.J. Brodie, N. Engl. J. Med., 342, 314 (2000); https://doi.org/10.1056/NEJM200002033420503
- T.R. Browne and G.L. Holmes, N. Engl. J. Med., 344, 1145 (2001); https://doi.org/10.1056/NEJM200104123441507
- R. Izzo, G. de Simone, R.B. Devereux, R. Giudice, M. De Marco, C.S. Cimmino, A. Vasta, N. De Luca and B. Trimarco, J. Hypertens., 29, 803 (2011); https://doi.org/10.1097/HJH.0b013e328343ce32
- G. Coppola, CNS Drugs, 18, 133 (2004); https://doi.org/10.2165/00023210-200418030-00001
- J.V. Murphy and A. Patil, CNS Drugs, 17, 101 (2003); https://doi.org/10.2165/00023210-200317020-00003
- T.-P. Ou-Yang, G.-M. Zhu, Y.-X. Ding, F. Yang, X.-L. Sun and W. Jiang, Neurochem. Res., 41, 933 (2016); https://doi.org/10.1007/s11064-015-1777-9
- H.A. Schenck, P.W. Lenkowski, I. Choudhury-Mukherjee, S.-H. Ko, J.P. Stables, M.K. Patel and M.L. Brown, Bioorg. Med. Chem., 12, 979 (2004); https://doi.org/10.1016/j.bmc.2003.12.011
- W.R. Dolbier Jr., J. Fluor. Chem., 126, 157 (2005); https://doi.org/10.1016/j.jfluchem.2004.09.033
- K. Grabowski, K.-H. Baringhaus and G. Schneider, Nat. Prod. Rep., 25, 892 (2008); https://doi.org/10.1039/b715668p
- K. Kumar and H. Waldmann, Angew. Chem. Int. Ed., 48, 3224 (2009); https://doi.org/10.1002/anie.200803437
- R.J. Nevagi, A.S. Dhake, H.I. Narkhede and P. Kaur, Bioorg. Chem., 54, 68 (2014); https://doi.org/10.1016/j.bioorg.2014.04.002
- B.E. Smart, J. Fluor. Chem., 109, 3 (2001); https://doi.org/10.1016/S0022-1139(01)00375-X
- V. Natchimuthu, K.A. Jayalatha and S. Ravi, J. Mol. Liq., 218, 120 (2016); https://doi.org/10.1016/j.molliq.2016.02.038
- B. Song, S. Yang, H. Zhong, L. Jin, D. Hu and G. Liu, J. Fluor. Chem., 126, 87 (2005); https://doi.org/10.1016/j.jfluchem.2004.10.041
- V. Natchimuthu, S. Thomas, M. Ramalingam and S. Ravi, J. Clin. Neurosci., 43, 82 (2017); https://doi.org/10.1016/j.jocn.2017.04.019
- S.-Y. Ooi and S. Ball, Prescriber, 20, 15 (2009); https://doi.org/10.1002/psb.538
- S.-Y. Ooi and S. Ball, Prescriber, 18, 48 (2007); https://doi.org/10.1002/psb.38
- M. Botta, S. Armaroli, D. Castagnolo, G. Fontana, P. Pera and E. Bombardelli, Bioorg. Med. Chem. Lett., 17, 1579 (2007); https://doi.org/10.1016/j.bmcl.2006.12.101
- A.A. Siddiqui, M.M. Abdullah, M. Arora, M. Islam and S.R. Ahmad, Indian drugs, 43, 790 (2006).
- S. Purser, P.R. Moore, S. Swallow and V. Gouverneur, Chem. Soc. Rev., 37, 320 (2008); https://doi.org/10.1039/B610213C
- B.A. Roecklein, H.J. Sacks, H. Mortko, N. Fluorofelbamate and J. Stables, J. Am. Soc. Exp. Neurotherap., 4, 97 (2007); https://doi.org/10.1016/j.nurt.2006.11.015
- G.W. Mathern, C. Cepeda, R.S. Hurst, J. Flores-Hernandez, D. Mendoza and M.S. Levine, Epilepsia, 41(suppl 7), 162 (2000); https://doi.org/10.1111/j.1528-1157.2000.tb01575.x
- M.J. Gunthorpe, C.H. Large and R. Sankar, Epilepsia, 53, 412 (2012); https://doi.org/10.1111/j.1528-1167.2011.03365.x
- V. Natchimuthu, S. Bandaru, A. Nayarisseri and S. Ravi, Comput. Biol. Chem., 64, 64 (2016); https://doi.org/10.1016/j.compbiolchem.2016.05.003
- J. Obniska, K. Kaminski, A. Zagorska, A. Dzierzawska-Majewska and J. Karolak-Wojciechowska, J. Fluor. Chem., 127, 417 (2006); https://doi.org/10.1016/j.jfluchem.2006.01.009
References
R.B. Aird, R.L. Masland and D.M. Woodbury, Epilepsy Res., 3, 77 (1989); https://doi.org/10.1016/0920-1211(89)90071-5
J.O. McNamara, Nature, 399, A15 (1999); https://doi.org/10.1038/399a015
R. Fisher, W.V.E. Boas, W. Blume, C. Elger, P. Genton, P. Lee and J. Engel, Epilepsia, 46, 470 (2005); https://doi.org/10.1111/j.0013-9580.2005.66104.x
T.K. Banerjee, B.K. Ray, S.K. Das, A. Hazra, M.K. Ghosal, T. Roy, A. Chaudhuri and D.K. Raut, Epilepsia, 51, 2384 (2010); https://doi.org/10.1111/j.1528-1167.2010.02740.x
S.I. Johannessen and C. Johannessen, Curr. Neuropharmacol., 8, 254 (2010); https://doi.org/10.2174/157015910792246254
S.M. Sisodiya, W.R. Lin, B.N. Harding, M.V. Squier and M. Thom, Brain, 125, 22 (2002); https://doi.org/10.1093/brain/awf002
A. Navale, S. Pawar, M. Deodhar and A. Kale, Med. Chem. Res., 22, 4316 (2013); https://doi.org/10.1007/s00044-012-0434-y
G. Kramer, Epilepsia, 42, 55 (2001); https://doi.org/10.1046/j.1528-1157.2001.042suppl.3055.x
P. Kwan and M.J. Brodie, N. Engl. J. Med., 342, 314 (2000); https://doi.org/10.1056/NEJM200002033420503
T.R. Browne and G.L. Holmes, N. Engl. J. Med., 344, 1145 (2001); https://doi.org/10.1056/NEJM200104123441507
R. Izzo, G. de Simone, R.B. Devereux, R. Giudice, M. De Marco, C.S. Cimmino, A. Vasta, N. De Luca and B. Trimarco, J. Hypertens., 29, 803 (2011); https://doi.org/10.1097/HJH.0b013e328343ce32
G. Coppola, CNS Drugs, 18, 133 (2004); https://doi.org/10.2165/00023210-200418030-00001
J.V. Murphy and A. Patil, CNS Drugs, 17, 101 (2003); https://doi.org/10.2165/00023210-200317020-00003
T.-P. Ou-Yang, G.-M. Zhu, Y.-X. Ding, F. Yang, X.-L. Sun and W. Jiang, Neurochem. Res., 41, 933 (2016); https://doi.org/10.1007/s11064-015-1777-9
H.A. Schenck, P.W. Lenkowski, I. Choudhury-Mukherjee, S.-H. Ko, J.P. Stables, M.K. Patel and M.L. Brown, Bioorg. Med. Chem., 12, 979 (2004); https://doi.org/10.1016/j.bmc.2003.12.011
W.R. Dolbier Jr., J. Fluor. Chem., 126, 157 (2005); https://doi.org/10.1016/j.jfluchem.2004.09.033
K. Grabowski, K.-H. Baringhaus and G. Schneider, Nat. Prod. Rep., 25, 892 (2008); https://doi.org/10.1039/b715668p
K. Kumar and H. Waldmann, Angew. Chem. Int. Ed., 48, 3224 (2009); https://doi.org/10.1002/anie.200803437
R.J. Nevagi, A.S. Dhake, H.I. Narkhede and P. Kaur, Bioorg. Chem., 54, 68 (2014); https://doi.org/10.1016/j.bioorg.2014.04.002
B.E. Smart, J. Fluor. Chem., 109, 3 (2001); https://doi.org/10.1016/S0022-1139(01)00375-X
V. Natchimuthu, K.A. Jayalatha and S. Ravi, J. Mol. Liq., 218, 120 (2016); https://doi.org/10.1016/j.molliq.2016.02.038
B. Song, S. Yang, H. Zhong, L. Jin, D. Hu and G. Liu, J. Fluor. Chem., 126, 87 (2005); https://doi.org/10.1016/j.jfluchem.2004.10.041
V. Natchimuthu, S. Thomas, M. Ramalingam and S. Ravi, J. Clin. Neurosci., 43, 82 (2017); https://doi.org/10.1016/j.jocn.2017.04.019
S.-Y. Ooi and S. Ball, Prescriber, 20, 15 (2009); https://doi.org/10.1002/psb.538
S.-Y. Ooi and S. Ball, Prescriber, 18, 48 (2007); https://doi.org/10.1002/psb.38
M. Botta, S. Armaroli, D. Castagnolo, G. Fontana, P. Pera and E. Bombardelli, Bioorg. Med. Chem. Lett., 17, 1579 (2007); https://doi.org/10.1016/j.bmcl.2006.12.101
A.A. Siddiqui, M.M. Abdullah, M. Arora, M. Islam and S.R. Ahmad, Indian drugs, 43, 790 (2006).
S. Purser, P.R. Moore, S. Swallow and V. Gouverneur, Chem. Soc. Rev., 37, 320 (2008); https://doi.org/10.1039/B610213C
B.A. Roecklein, H.J. Sacks, H. Mortko, N. Fluorofelbamate and J. Stables, J. Am. Soc. Exp. Neurotherap., 4, 97 (2007); https://doi.org/10.1016/j.nurt.2006.11.015
G.W. Mathern, C. Cepeda, R.S. Hurst, J. Flores-Hernandez, D. Mendoza and M.S. Levine, Epilepsia, 41(suppl 7), 162 (2000); https://doi.org/10.1111/j.1528-1157.2000.tb01575.x
M.J. Gunthorpe, C.H. Large and R. Sankar, Epilepsia, 53, 412 (2012); https://doi.org/10.1111/j.1528-1167.2011.03365.x
V. Natchimuthu, S. Bandaru, A. Nayarisseri and S. Ravi, Comput. Biol. Chem., 64, 64 (2016); https://doi.org/10.1016/j.compbiolchem.2016.05.003
J. Obniska, K. Kaminski, A. Zagorska, A. Dzierzawska-Majewska and J. Karolak-Wojciechowska, J. Fluor. Chem., 127, 417 (2006); https://doi.org/10.1016/j.jfluchem.2006.01.009