Conformationally restricted goniofufurone mimics with halogen, azido or benzoyloxy groups at the C-7 position: Design, synthesis and antiproliferative activity
Creators
- 1. Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia
- 2. Oncology Institute of Vojvodina, Faculty of Medicine, University of Novi Sad, Put Dr Goldmana 4, 21204 Sremska Kamenica, Serbia
- 3. Institute for Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia
- 4. Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia; Serbian Academy of Sciences and Arts, Knez Mihajlova 35, 11000 Belgrade, Serbia
Description
A series of new conformationally restricted goniofufurone mimics, bearing an additional 1,3-dioxan ring and a halogen, azido or benzoyloxy functionality at the C-7 position has been designed and synthesized. The Appel reaction was used for replacement of 7-OH group with Cl or Br functions in tricyclic lactone (3). 7-Iodo derivative (3d) was prepared by using the Ph3P/I2/2,6-lutidine reagent system. 7-Fluoro group was introduced by treatment of 3 with DAST, while the corresponding 7-azido and 7-benzoyloxy derivatives have been prepared by multistep sequences. Synthesized products were evaluated for their ability to inhibit growth of selected human malignant cell lines. Structure-activity relationships demonstrated that the nature of a substituent at the C-7 position could enhance the antiproliferative activity of the analogues. The preliminary study on the mechanisms indicated that all synthesized compounds induced apoptosis in 61–77% of K562 cells.
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- 0040-4020 (ISSN)
Funding
- Ministry of Education, Science and Technological Development
- Synthesis and biological testing of new mimics or derivatives of selected cytotoxic lactones, antitumor agent tiazofurin and natural naphthenic acids 172006