Format

Send to

Choose Destination
Medchemcomm. 2018 Aug 16;9(10):1708-1714. doi: 10.1039/c8md00352a. eCollection 2018 Oct 1.

7-Deacetyl-10-alkylthiocolchicine derivatives - new compounds with potent anticancer and fungicidal activity.

Author information

1
Faculty of Chemistry , Adam Mickiewicz University , Umultowska 89b , 61-614 Poznań , Poland . Email: joankur@amu.edu.pl ; Email: pbar@amu.edu.pl ; Email: beatakoz@amu.edu.pl.
2
Wood Technology Institute , Environmental Protection and Wood Chemistry Department , Winiarska 1 , 60-654 Poznan , Poland . Email: kwasniewskapatrycja@gmail.com.
3
Department of Toxicology , Poznan University of Medical Sciences , Dojazd 30 , 60-631 Poznań , Poland . Email: myszkowski.krzysztof.a@gmail.com ; Email: marek.murias@ump.edu.pl.
4
Institute of Chemical Wood Technology , University of Life Science , Wojska Polskiego 38/42 , 60-037 Poznań , Poland . Email: gcofta@gmail.com.
5
Department of Medicinal Chemistry , Institute of Pharmacology , Polish Academy of Sciences , Smętna 12 , 31-343 Kraków , Poland . Email: rkurczab@gmail.com.

Abstract

A series of new semi-synthetic 7-deacetyl-10-alkylthiocolchicne derivatives with ethyl, n-propyl, i-propyl and n-butyl substituents were synthesised and characterised by spectroscopic methods, elemental analysis, DFT calculations and molecular docking simulations. All the synthesized compounds have been tested for fungicidal and anticancer activities against SKOV-3, LoVo, MCF-7, MDA-MB-231 and the lung-derived fibroblast CCD39Lu. All the new colchicine derivatives exhibit significantly higher cytotoxicity towards the SKOV-3 tumour cell line than the natural product - colchicine. The most effective cytotoxic agents were 7-deacetyl-10-n-buthylthiocolchicine and 7-deacetyl-10-i-propylthiocolchicine. Among all the compounds tested, 7-deacetyl-10-n-buthylthiocolchicine exhibited the highest fungicidal activity. Molecular modeling indicated that several mutations found in the β-tubulin unit of the tested fungal strains are crucial for antifungal activity and selectivity of 7-deacetyl-10-n-buthylthiocolchicine. The obtained results may be useful for the development of selective colchicine derivatives as effective fungicidal and/or anticancer drugs.

PMID:
30429975
PMCID:
PMC6195099
[Available on 2019-08-16]
DOI:
10.1039/c8md00352a

Supplemental Content

Full text links

Icon for Royal Society of Chemistry
Loading ...
Support Center