title: Synthesis of pro-apoptotic indapamide derivatives as anticancer agents.
abstract: 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 µM. 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 µM 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 µM.
authors: a TUBITAK Marmara Research Center, Materials Institute Gebze , Kocaeli , Turkey .
authors: Özgür
authors: Ö
authors: Yılmaz
authors: b Department of Pharmaceutical Biotechnology, Faculty of Pharmacy , Marmara University , Haydarpaşa , İstanbul , Turkey .
authors: Suna
authors: S
authors: Özbaş Turan
authors: b Department of Pharmaceutical Biotechnology, Faculty of Pharmacy , Marmara University , Haydarpaşa , İstanbul , Turkey .
authors: Jülide
authors: J
authors: Akbuğa
authors: c Department of Biophysics , School of Medicine, Marmara University , Haydarpaşa , İstanbul , Turkey .
authors: Pınar Mega
authors: PM
authors: Tiber
authors: c Department of Biophysics , School of Medicine, Marmara University , Haydarpaşa , İstanbul , Turkey .
authors: Oya
authors: O
authors: Orun
authors: d Laboratorio di Chimica Bioinorganica , Università degli Studi di Firenze , Sesto Fiorentino (Firenze) , Italy , and.
authors: Claudiu T
authors: CT
authors: Supuran
authors: e Department of Pharmaceutical Chemistry, Faculty of Pharmacy , Marmara University , Haydarpaşa , İstanbul , Turkey.
authors: Ş Güniz
authors: ŞG
authors: Küçükgüzel
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003124:Colorimetry; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007190:Indapamide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002257:Carbonic Anhydrase Inhibitors; D002256:Carbonic Anhydrases; D007190:Indapamide
keywords: 4-thiazolidinone; Apoptosis; indapamide; sulfonamide; sulphonylthiourea