title: Synthesis and QSAR study of novel cytotoxic spiro[3H-indole-3,2'(1'H)-pyrrolo[3,4-c]pyrrole]-2,3',5'(1H,2'aH,4'H)-triones.
abstract: 1,3-Dipolar cycloaddition reaction of 1-aryl-1H-pyrrole-2,5-diones 1a-e with non-stabilized azomethine ylides, generated in situ via decarboxylative condensation of isatins 2a-c and sarcosine (3) in refluxing ethanol, afforded 4'-aryl-5'a,6'-dihydro-1'-methyl-spiro[3H-indole-3,2'(1'H)-pyrrolo[3,4-c]pyrrole]-2,3',5'(1H,2'aH,4'H)-triones 4a-o in good yields. Compound 4l exhibited high anti-tumor activity against HEPG2 (liver cancer) cell line (IC(50) = 12.16 μM) compared to that of Doxorubicin (IC(50) = 7.36 μM), and the other synthesized compounds revealed moderate anti-tumor properties against HCT116 (colon), MCF7 (breast) and HEPG2 (liver) human tumor cell lines. 3D-Pharmacophore modeling and quantitative structure-activity relationship (QSAR) analysis were combined to explore the structural requirements controlling the observed anti-tumor properties. It was found that the major structural factors affecting potency of these compounds were related to their basic skeleton.
authors: Pesticide Chemistry Department, National Research Centre, Dokki, Cairo 12622, Egypt. girgisas10@yahoo.com
authors: Adel S
authors: AS
authors: Girgis
authors: Jacek
authors: J
authors: Stawinski
authors: Nasser S M
authors: NS
authors: Ismail
authors: Hanaa
authors: H
authors: Farag
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D020128:Inhibitory Concentration 50; D011758:Pyrroles / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D015203:Reproducibility of Results; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D011758:Pyrroles; D013141:Spiro Compounds