RATIONAL DESIGN, SYNTHESIS AND IN VITRO EVALUATION OF N-(4-ETHOXYPHENYLSULFONYL)-L-GLUTAMIC ACID ANALOGUES AS ANTIANGIOGENIC AND ANTICANCER AGENTS ON MULTIPLE MYELOMA
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Published:2021-04-20
Issue:12
Volume:57
Page:26-35
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ISSN:0019-462X
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Container-title:INDIAN DRUGS
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language:
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Short-container-title:IND. DRU.
Author:
Saha Abhijit1, Sarker Koushik, Ghosh Avijit, Mishra Suvasish, Sen Subrata,
Affiliation:
1. A.P.C.Ray Memorial Cancer Chemotherapeutic Research Unit, College of Pharmaceutical Sciences, Mohuda, Berhampur, Odisha, PIN-760002, INDIA
Abstract
We report the rational design, synthesis and evaluation of the anticancer and antiangiogenic activity of the N-(4-ethoxyphenylsulfonyl)-L-glutamic acid analogs on multiple myeloma. From the series, compound 2c, 2f, and 2h exhibit cytotoxic action on human multiple myeloma cell line RPMI8226 with IC50 (μM) value 2.72, 2.24, and 1.81, respectively. These compounds possess 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 kidney epithelial cell (VERO), respectively. The compounds also have an antiproliferative effect on HUVECs, which was carried out using the dye exclusion method with trypan blue. Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) Tyr-1175 phosphorylation inhibition assay showed compound 2f, and 2h to be the active inhibitors of roangiogenic responses mediated by VEGFR-2. A molecular docking study of 2f with VEGFR-2 showed possible interaction with a binding energy of -74.19 kcal/mol.
Publisher
Indian Drug Manufacturers' Association (IDMA)
Subject
Drug Discovery,Pharmaceutical Science,Pharmacology
Reference24 articles.
1. 1) Fairfield H., Falank C., Avery L., Reagan M.R.: Multiple myeloma in the marrow: pathogenesis and treatments. Ann N Y Acad Sci. 2016, 1364, 32-51. 2. 2) Tucker W L., Thomas FT.: B lymphocytes: how they develop and function. Blood. 2008,112,1570-1580. 3. 3) Rajkumar S.V., Mesa R.A., Fonseca R., Schroeder G., Plevak M.F., Dispenzieri A., Lacy M.Q., Lust J.A., Witzig T.E., Gertz M.A., Kyle R.A., Russell S.J., Greipp P.R.: Bone marrow angiogenesis in 400 patients with monoclonal gammopathy of undetermined significance, multiple myeloma, and primary amyloidosis. Clin Cancer Res. 2002, 8, 2210-2216. 4. 4) Ria R., Vacca A., Russo F., Cirulli T., Massaia M., Tosi P., Cavo M., Guidolin D., Ribatti D., Dammacco F.: A VEGF-dependent autocrine loop mediates proliferation and capillarogenesis in bone marrow endothelial cells of patients with multiple myeloma. Thromb Haemost. 2004 , 92, 1438-1445. 5. 5) Vacca A., Ria R., Semeraro F., Merchionne F., Coluccia M., Boccarelli A., Scavelli C., Nico B., Gernone A., Battelli F., Tabilio A., Guidolin D., Petrucci M.T., Ribatti D., Dammacco F.: Endothelial cells in the bone marrow of patients with multiple myeloma. Blood. 2003, 102, 3340-3348.
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