title: Design, synthesis and QSAR studies of dispiroindole derivatives as new antiproliferative agents.
abstract: A variety of 4'-aryl-3-(arylmethylidene)-1″-[(cyclic-amino)methylene]-1'-methyl-dispiro[cyclohexane-1,3'-pyrrolidine-2',3″-[3H]indole]-2,2″(1″H)-diones 4a-u were prepared via reaction of 2E,6E-bis(arylidene)-1-cyclohexanones 1a-i with azomethine ylides, generated in situ via a decarboxylative condensation of isatins 2a-c and sarcosine (3). Single crystal X-ray study of 4a, revealed structural and stereochemical features of these derivatives. While most of the synthesized compounds exhibit mild antitumor properties when tested against various human tumor cell lines (HEPG2 "liver", HELA "cervical" and PC3 "prostate" cancers), three of them, 4d and 4p (active against HEPG2), and compound 4g (active against HELA), demonstrated higher activities, that were close or even higher than that of the reference standard Doxorubicin. QSAR studies revealed good predictive and statistically significant 3 descriptor models (r2=0.903-0.812, r2adjusted=0.855-0.672, r2prediction=0.773-0.605).
authors.affiliation: Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Riham F
authors.initials: RF
authors.lastname: George
authors.forename: Nasser S M
authors.initials: NS
authors.lastname: Ismail
authors.forename: Jacek
authors.initials: J
authors.lastname: Stawinski
authors.forename: Adel S
authors.initials: AS
authors.lastname: Girgis
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D013141:Spiro Compounds; D004317:Doxorubicin; C030374:indole
keywords: 2,6-Bis(arylidene)-1-cyclohexanone; Antitumor; Azomethine ylide; QSAR; Spiropyrrolidine-oxindole