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Design, synthesis and biological evaluation of novel steroidal spiro-oxindoles as potent antiproliferative agents.
- Source :
-
The Journal of steroid biochemistry and molecular biology [J Steroid Biochem Mol Biol] 2014 May; Vol. 141, pp. 121-34. Date of Electronic Publication: 2014 Feb 06. - Publication Year :
- 2014
-
Abstract
- Two series of novel steroidal spiro-pyrrolidinyl oxindoles 3a-t and 6a-c were designed and synthesized from dehydroepiandrosterone using the 1,3-dipolar cycloaddition as the key step and further evaluated for their antiproliferative activities for four human cancer cell lines (MGC-803, EC109, SMMC-7721 and MCF-7). This protocol achieved the formation of two CC bonds, one CN bond and the creation of one new five-membered pyrrolidine ring and three contiguous stereocenters in a single operation. Biological evaluation showed that these synthesized steroidal spiro-pyrrolidinyl oxindoles possessed moderate to good antiproliferative activities against the tested cell lines and some of them were more potent than 5-Fu. Particularly, compound 3g showed good antiproliferative activity against SMMC-7721 (IC50=0.71μM). Steroid dimer 6b showed improved antiproliferative activities against SMMC-7721 and MCF-7 with the IC50 values of 4.30 and 2.06μM, respectively. Flow cytometry analysis demonstrated that compound 3n caused the cellular early apoptosis and cell cycle arrest at G2/M phase in a concentration- and time-dependent manner. [Corrected]<br /> (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Subjects :
- Antineoplastic Agents chemical synthesis
Apoptosis drug effects
Cell Cycle Checkpoints drug effects
Cell Line, Tumor
Cell Proliferation drug effects
Cycloaddition Reaction
Drug Design
Drug Screening Assays, Antitumor
Humans
Indoles chemical synthesis
Indoles pharmacology
Ketosteroids chemical synthesis
Pyrrolidines chemical synthesis
Spiro Compounds chemical synthesis
Antineoplastic Agents pharmacology
Ketosteroids pharmacology
Pyrrolidines pharmacology
Spiro Compounds pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-1220
- Volume :
- 141
- Database :
- MEDLINE
- Journal :
- The Journal of steroid biochemistry and molecular biology
- Publication Type :
- Academic Journal
- Accession number :
- 24508598
- Full Text :
- https://doi.org/10.1016/j.jsbmb.2014.01.015