101. Design, synthesis and QSAR studies of dispiroindole derivatives as new antiproliferative agents.
- Author
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George RF, Ismail NS, Stawinski J, and Girgis AS
- Subjects
- Cell Line, Tumor, Cell Proliferation drug effects, Crystallography, X-Ray, Doxorubicin chemistry, Doxorubicin pharmacology, Humans, Inhibitory Concentration 50, Molecular Structure, Spiro Compounds chemical synthesis, Spiro Compounds chemistry, Spiro Compounds pharmacology, Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Drug Design, Indoles chemical synthesis, Indoles chemistry, Indoles pharmacology, Quantitative Structure-Activity Relationship
- 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)., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)
- Published
- 2013
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