Design, synthesis and QSAR studies of dispiroindole derivatives as new antiproliferative agents
2013 (English)In: European Journal of Medicinal Chemistry, ISSN 0223-5234, E-ISSN 1768-3254, Vol. 68, 339-351 p.Article in journal (Refereed) Published
A variety of 4'-ary1-3-(arylmethylidene)-1 ''-[(cyclic-amino)methylene]-1'-methyl-dispiro[cyclohexane-1,3'-pyrrolidine-2',3 ''-[3H]indole]-2,2 ''(1H)-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 PD 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 (r(2) = 0.903-0.812, r(adjusted)(2) = 0.855-0.672, r(prediction)(2) = 0.773-0.605).
Place, publisher, year, edition, pages
2013. Vol. 68, 339-351 p.
2, 6-Bis(arylidene)-1-cydohexanone, Spiropyrrolidine-oxindole, Azomethine ylide, Antitumor, QSAR
Pharmacology and Toxicology
IdentifiersURN: urn:nbn:se:su:diva-98095DOI: 10.1016/j.ejmech.2013.07.035ISI: 000326902300036OAI: oai:DiVA.org:su-98095DiVA: diva2:682308
FunderSida - Swedish International Development Cooperation Agency