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Design, Synthesis, Molecular Docking and in vitro Evaluation of N-(4-Ethoxyphenylsulfonyl)pyrrolidine-2-carboxylic Acid Analogues as Antiangiogenic and Anticancer Agents on Multiple Myeloma
Corresponding Author(s) : S. Sen
Asian Journal of Chemistry,
Vol. 33 No. 4 (2021): Vol 33 Issue 4
Abstract
In present work, N-(4-ethoxyphenylsulfonyl)pyrrolidine-2-carboxylic acid analogs were designed, synthesized and biologically evaluated as an antiangiogenic and anticancer agent on multiple myeloma. Compounds 3i, 3k and 3m exhibited the cytotoxic action on human multiple myeloma cell line RPMI8226 with IC50 (μM) value 3.72, 3.89 2.28, respectively. These compounds possessed the antiangiogenic property and are selectively cytotoxic to cancer cells, as observed from the in vitro study of human umbilical vein endothelial cell (HUVEC) and African green monkey epithelial cell (VERO), respectively. Antiproliferative assay of the compounds on HUVECs was carried out using the dye exclusion method with trypan blue. Molecular docking study of compound 3m with vascular endothelial growth factor receptor-2 (VEGFR-2) showed possible interaction with a binding energy -62.27 kcal/mol.
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- Chemical Structure Drawing Standard, Cambridge Soft Corporation, USA (2010).
- E. Fischer and A. Speier, Chem. Ber., 28, 3252 (1895); https://doi.org/10.1002/cber.189502803176
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S.V. Rajkumar and R.A. Kyle, Mayo Clin. Proc., 80, 1371 (2005); https://doi.org/10.4065/80.10.1371
M. Seifert and R. Küppers, Leukemia, 30, 2283 (2016); https://doi.org/10.1038/leu.2016.226
C.A. Janeway Jr., P. Travers, M. Walport and M.J. Shlomchik, The Immune System in Health and Disease, Immunobiology, Garland Science: New York, edn 5 (2001).
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.K. Kumar, J.R. Mikhael, F.K. Buadi, D. Dingli, A. Dispenzieri, R. Fonseca, M.A. Gertz, P.R. Greipp, S.R. Hayman, R.A. Kyle, M.Q. Lacy, J.A. Lust, C.B. Reeder, V. Roy, S.J. Russell, K.E.D. Short, A.K. Stewart, T.E. Witzig, S.R. Zeldenrust, R.J. Dalton, S.V. Rajkumar and P.L.Bergsagel, Mayo Clin. Proc., 84, 1095 (2009); https://doi.org/10.4065/mcp.2009.0603
A. Vacca, D. Ribatti, M. Presta, M. Minischetti, M. Iurlaro, R. Ria, A. Albini, F. Bussolino and F. Dammacco, Blood, 93, 3064 (1999); https://doi.org/10.1182/blood.V93.9.3064
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N. Giuliani, P. Storti, M. Bolzoni, B.D. Palma and S. Bonomini, Cancer Microenviron., 4, 325 (2011); https://doi.org/10.1007/s12307-011-0072-9
A. Ferrucci, M. Moschetta, M.A. Frassanito, S. Berardi, I. Catacchio, R. Ria, V. Racanelli, A. Caivano, A.G. Solimando, D. Vergara, M. Maffia, D. Latorre, A. Rizzello, A. Zito, P. Ditonno, E. Maiorano, D. Ribatti and A. Vacca, Clin. Cancer Res., 20, 5796 (2014); https://doi.org/10.1158/1078-0432.CCR-14-0847
M. Moschetta, A. Basile, A. Ferrucci, M.A. Frassanito, L. Rao, R. Ria, A.G. Solimando, N. Giuliani, A. Boccarelli, F. Fumarola, M. Coluccia, B. Rossini, S. Ruggieri, B. Nico, E. Maiorano, D. Ribatti, A.M. Roccaro and A. Vacca, Clin. Cancer Res., 19, 4371 (2013); https://doi.org/10.1158/1078-0432.CCR-13-0039
M. Shibuya, Endothelium, 13, 63 (2006); https://doi.org/10.1080/10623320600697955
H. Goldschmidt, J. Ashcroft, Z. Szabo and L. Garderet, Ann. Hematol., 98, 1 (2019); https://doi.org/10.1007/s00277-018-3546-8
S.V. Rajkumar and S. Kumar, Blood Cancer J., 10, 94 (2020); https://doi.org/10.1038/s41408-020-00359-2
P. Kapoor, V. Ramakrishnan and S.V. Rajkumar, Semin. Hematol., 49, 228 (2012); https://doi.org/10.1053/j.seminhematol.2012.04.010
S. Ciolli, F. Leoni, C. Casini, C. Breschi, V. Santini and A. Bosi, Br. J.Haematol., 141, 814 (2008); https://doi.org/10.1111/j.1365-2141.2008.07147.x
K. Sarker, A. Ghosh, S. Mishra, A. Saha and S. Sen, Asian J. Chem., 32, 12 (2020); https://doi.org/10.14233/ajchem.2020.22957
Chemical Structure Drawing Standard, Cambridge Soft Corporation, USA (2010).
E. Fischer and A. Speier, Chem. Ber., 28, 3252 (1895); https://doi.org/10.1002/cber.189502803176
M. Boncler, M. Rozalski, U. Krajewska, A. Podsêdek and C. Watala, J. Pharmacol. Tox. Met., 69, 9 (2014); https://doi.org/10.1016/j.vascn.2013.09.003
T. Mosmann, J. Immunol. Methods, 65, 55 (1983); https://doi.org/10.1016/0022-1759(83)90303-4
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
B.I.O.V.I.A. Dassault Systèmes, Discovery Studio, 4.1, San Diego: Dassault Systèmes (2017).
S.N. Rao, M.S. Head, A. Kulkarni and J.M. Lalonde, J. Chem. Inf. Model., 47, 2159 (2007); https://doi.org/10.1021/ci6004299