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ÖZBAŞ, SUNA

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Author: KÜÇÜKGÜZEL, ŞÜKRİYE GÜNİZ × Subject: ANTI-HCV ×

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    PublicationOpen Access
    Synthesis of pro-apoptotic indapamide derivatives as anticancer agents
    (TAYLOR & FRANCIS LTD, 2015-11-02) ORUN, OYA; Yilmaz, Ozgur; Turan, Suna Ozbas; Akbuga, Julide; Tiber, Pinar Mega; Orun, Oya; Supuran, Claudiu T.; Kucukguzel, S. Guniz
    4-Chloro-3-({[(substitutedamino)carbonothioyl]amino} sulfonyl)-N-(2-methyl-2,3-dihydro-1H-indole-1-yl)benzamide (1-20) and 4-chloro-3-({[3-(substituted)-4-oxo-1,3-thiazolidine-2-ylidene]amino} sulfonyl)-N-(2-methyl-2,3-dihydro-1H-indole-1-yl)benzamide derivatives (21-31) were synthesized from 4-chloro-N-(2-methyl-2,3-dihydroindol-1-yl)-3-sulfamoylbenzamide (indapamide). 4-Chloro-3-({[(4-chlorophenyl)amino)carbonothioyl]amino} sulfonyl)-N-(2-methyl- 2,3-dihydro-1H-indole-1-yl)benzamide 12 demonstrated the highest proapoptotic activity among all synthesized compounds on melanoma cell lines MDA-MB-435 with 3.7% growth inhibition at the concentration of 10 mu M. Compound 12 (SGK 266) was evaluated in vitro using the MTT colorimetric method against melanoma cancer cell line MDA-MB435 growth inhibition for different doses and exhibited anticancer activity with IC50 values of 85-95 mu M against melanoma cancer cell line MDA-MB435. In addition, this compound was investigated as inhibitors of four physiologically relevant human carbonic anhydrase isoforms, hCA I, II, IX and XII. The compund inhibited these enzymes with IC50 values ranging between 0.72 and 1.60 mu M.