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Design, Synthesis and in vitro Evaluation of 2-(Quinoline-8-sulfonamido)pentanedioic Acid Analogues as Antiangiogenic and Antitumor Agents on Multiple Myeloma
Corresponding Author(s) : Subrata Sen
Asian Journal of Chemistry,
Vol. 33 No. 8 (2021): Vol 33 Issue 8, 2021
Abstract
Thalidomide is presently approved as antiangiogenic and anticancer drug in multiple myeloma. The authors present a number of analogue-based designs of N-(o-carboxybenzoyl)-DL-glutamic acid, a major thalidomide metabolite. The compounds were synthesized and biologically tested in multiple myeloma as anticancer agents. Three compounds inhibited HUVEC proliferation at low micromolar concentrations, indicating that they are antiangiogenic and cytotoxic to human multiple myeloma RPMI8226. The active compounds were tested for antiproliferative activity on HUVECs using the dye exclusion method with trypan blue. Dimethyl-2-(quinoline-8-sulfonamido)pentanedioate (2c), in particular, inhibits VEGFR-2 phosphorylation at the Tyr-1175 residue, as determined by SDS PAGE. The binding mode of (2c) was predicted in silico in order to better understand how it interacts with essential amino acid residues in the VEGFR-2 active site. The binding energy was calculated as -161.41 kcal/mol. in vitro Study of the compounds on the Vero cell line shows less toxicity towards the normal endothelial cells than the cancer cells.
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H. Quach, D. Ritchie, A.K. Stewart, P. Neeson, S. Harrison, N.J. Smyth and H.M. Prince, Leukemia, 24, 22 (2010); https://doi.org/10.1038/leu.2009.236
J.W. Faigle, H. Keberle, W. Riess and K. Schmid, Experientia, 18, 389 (1962); https://doi.org/10.1007/BF02151479
F. Kemper and Z. Gesamte, Exp. Med., 135, 454 (1962); https://doi.org/10.1007/BF02045211
F. Kallinowski, S. Runkel, H.P. Fortmeyer, H. Forster and P. Vaupel, J. Cancer Res. Clin. Oncol., 113, 209 (1987); https://doi.org/10.1007/BF00396375
J.M. Mates, J.A. Segura, M. Martin-Rufian, J.A. Campos-Sandoval, F.J. Alonso and J. Marquez, Curr. Mol. Med., 13, 514 (2013); https://doi.org/10.2174/1566524011313040005
S. Graff, D. Rittenberg and G.L. Foster, J. Biol. Chem., 133, 745 (1940); https://doi.org/10.1016/S0021-9258(18)73305-X
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M.L. Eidinoff, J.E. Knoll, B. Marano and L. Cheong, Cancer Res., 18, 105 (1958).
A. Efeyan and D.M. Sabatini, Curr. Opin. Cell Biol., 22, 169 (2010); https://doi.org/10.1016/j.ceb.2009.10.007
N. Hosokawa, T. Sasaki, S. Iemura, T. Natsume, N. Mizushima and T. Hara, Autophagy, 5, 973 (2009); https://doi.org/10.4161/auto.5.7.9296
B.E. Leach, J.H. Ford and A.J. Whiffen, J. Am. Chem. Soc., 69, 474 (1947); https://doi.org/10.1021/ja01194a519
J.B. Field, A. Mireless, H.R. Pachl, L. Bascoy, L. Cano and W.K. Bullock, Antibiot. Annu., 6, 572 (1959).
C.G. Smith, W.L. Lummis and J.E. Grady, Cancer Res., 20, 1394 (1960).
R. Catane, D.D. Von Hoff, D.L. Glaubiger and F.M. Muggia, Cancer Treat. Rep., 63, 1033 (1979); https://doi.org/10.1016/S0305-7372(79)80004-3
J. Folkman, N. Engl. J. Med., 285, 404 (1971); https://doi.org/10.1056/NEJM197108122850711
N. Ferrara, H. Gerber and J. LeCouter, Nat. Med., 9, 669 (2003); https://doi.org/10.1038/nm0603-669
H. Fairfield, C. Falank, L. Avery and M.R. Reagan, Ann. N. Y. Acad. Sci., 1364, 32 (2016); https://doi.org/10.1111/nyas.13038
S. Sen, K. Sarker, A. Ghosh, S. Mishra, A. Saha, D. Goswami, T. Jha, J.K. Gupta and A.U. De, Int. J. Pharm. Sci. Rev. Res., 10, 118 (2011).
S. Sen, K. Sarker, A. Ghosh, S. Mishra, A. Saha, D. Goswami, J.K. Gupta and A.U. De, Asian J. Chem., 24, 1872 (2012).
K. Sarker, A. Ghosh, S. Mishra, A. Saha and S. Sen, Asian J. Chem., 32, 3079 (2020); https://doi.org/10.14233/ajchem.2020.22957
A. Ghosh, A. Saha, K. Sarker, S. Mishra and S. Sen, Asian J. Chem., 33, 727 (2021); https://doi.org/10.14233/ajchem.2021.23064
L.F. Lindoy and S.E. Livingstone, Aust. J. Chem., 17, 820 (1964); https://doi.org/10.1071/CH9640820
A.I. Vogel, Aliphatic compounds, In: Vogel’s Textbook of Practical Organic Chemistry, ELBS with Longman, edn 5, pp. 696 & 701 (1989).
T. Mosmann, J. Immunol. Methods, 65, 55 (1983); https://doi.org/10.1016/0022-1759(83)90303-4
M. Boncler, M. Rozalski, U. Krajewska, A. Podsedek and C. Watala, J. Pharmacol. Toxicol. Methods, 69, 9 (2014); https://doi.org/10.1016/j.vascn.2013.09.003
G. Malich, B. Markovic and C. Winder, Toxicology, 124, 179 (1997); https://doi.org/10.1016/S0300-483X(97)00151-0
W. Strober, Curr. Protoc. Immunol., 111, A3.B.1 (2015); https://doi.org/10.1002/0471142735.ima03bs111
STATISTICA (data analysis software system), version 8.0, StatSoft, Inc. (2008).
J. Brants, K. Semenchenko, C. Wasylyk, A. Robert, A. Zambrano, A. Carles, K. Pradeau-Aubreton, C. Birck, J.A. Schalken, O. Poch, J. de Mey and B. Wasylyk, PLoS One, 7, e51258 (2012); https://doi.org/10.1371/journal.pone.0051258
BIOVIA Dassault Systèmes, Discovery Studio, 4.1, Dassault Systèmes: San Diego (2017).
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