Rational design, synthesis, and 2D-QSAR study of anti-oncological alkaloids against hepatoma and cervical carcinoma

Siva S. Panda, Peter J. Steel

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Antitumor active dispiro[3H-indole-3,2′-pyrrolidine-3′,3′′-piperidine]-2(1H),4′′-diones 11-19 were regioselectively synthesized via azomethine ylide cycloaddition reactions with 3E,5E-1-alkyl-3,5-bis(arylmethylidene)-4-piperidones 3-7. Compounds 13, 14, and 16 reveal higher potency against the HeLa (cervical) tumor cell line than the standard reference cisplatin, while 11, and 12 seem more potent against the HepG2 (liver) carcinoma cell line relative to the standard reference doxorubicin hydrochloride as determined by in vitro Sulfo-Rhodamine-B bio-assay. 3D-Pharmacophores of the HeLa comprise five chemical features viz., two hydrogen bond acceptors, two hydrophobic centers and one positive ionizable center and HepG2 contains three chemical features viz., a hydrogen bond acceptor, a hydrophobic center and a positive ionizable center. These features of the tumor cell lines explain the variation of bioactivity relative to chemical structure. Statistically significant QSAR models describing the spiro-alkaloid bio-properties were obtained employing CODESSA-Pro software validating the observed pharmacological observations and identifying the most important parameters governing activity.

Original languageEnglish (US)
Pages (from-to)28554-28569
Number of pages16
JournalRSC Advances
Volume5
Issue number36
DOIs
StatePublished - Mar 5 2015
Externally publishedYes

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Alkaloids
rhodamine B
Cells
Tumors
Hydrogen bonds
Piperidones
Cycloaddition
Bioassay
Bioactivity
Liver
Doxorubicin
Cisplatin

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

Cite this

Rational design, synthesis, and 2D-QSAR study of anti-oncological alkaloids against hepatoma and cervical carcinoma. / Panda, Siva S.; Steel, Peter J.

In: RSC Advances, Vol. 5, No. 36, 05.03.2015, p. 28554-28569.

Research output: Contribution to journalArticle

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