Synthesis and biological evaluation of new steroidal pyridines as potential anti-prostate cancer agents

Synthesis and biological evaluation of new steroidal pyridines as potential anti-prostate cancer... A series of new steroidal pyridines have been synthesized through the based-promoted three-component reaction and preliminarily evaluated for their antiproliferative activity against different types of cancer cell lines. SARs studies showed that the heterocyclic rings attached to the 4-position of the pyridine ring were preferred over the phenyl rings for the activity. Among these compounds, the most potent compound exhibited good growth inhibition against all the tested cancer cells, especially for PC-3 cells with an IC50 value of 1.55 μM. Further mechanistic studies revealed that the most potent compound inhibited colony formation, migration and evasion of PC-3 cells in a concentration-dependent manner as well as induced apoptosis of PC-3 cells possibly through the mitochondria-related apoptotic pathways. Caspase-3/-9 and PARP were activated, finally leading to the apoptosis of PC-3 cells. For the androgen-sensitive (AR+) prostate cancer cell line LNCaP, the most potent compound was less potent than abiraterone with the IC50 value of 8.48 and 3.29 μM, respectively. The most potent compound could be used as a starting point for the development of new steroidal heterocycles with improved anticancer potency and selectivity. The synthesized steroidal pyridines contain the functional -OEt and CN groups, which could be used for further modifications for the construction of the steroid library. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Medicinal Chemistry Elsevier

Synthesis and biological evaluation of new steroidal pyridines as potential anti-prostate cancer agents

Synthesis and biological evaluation of new steroidal pyridines as potential anti-prostate cancer agents

European Journal of Medicinal Chemistry 145 (2018) 11e22 Contents lists available at ScienceDirect European Journal of Medicinal Chemistry journal homepage: http://www.elsevier.com/locate/ejmech Research paper Synthesis and biological evaluation of new steroidal pyridines as potential anti-prostate cancer agents a, b, c, d, 1 a, b, c, d, 1 a, b, c, d a, b, c, d Yun-Kai Shi , Bo Wang , Xiao-Li Shi , Yuan-Di Zhao , a, b, c, d, * a, b, c, d, ** Bin Yu , Hong-Min Liu Key Laboratory of Advanced Drug Preparation Technologies (Zhengzhou University), Ministry of Education, PR China Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, PR China School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China Key Laboratory of Henan Province for Drug Quality and Evaluation, PR China art i cle i nfo abstract Article history: A series of new steroidal pyridines have been synthesized through the based-promoted three-compo- Received 23 October 2017 nent reaction and preliminarily evaluated for their antiproliferative activity against different types of Received in revised form cancer cell lines. SARs studies showed that the heterocyclic rings attached to the 4-position of the 29 December 2017 pyridine ring were preferred over the phenyl rings for the activity. Among these compounds, the most Accepted 30 December 2017 potent compound exhibited good growth inhibition against all the tested cancer cells, especially for PC- Available online 2 January 2018 3 cells with an IC value of 1.55 mM. Further mechanistic studies revealed that the most potent com- pound inhibited colony formation, migration and evasion of PC-3 cells in a concentration-dependent Keywords: manner as well as induced apoptosis of PC-3 cells possibly through the mitochondria-related apoptotic Steroids pathways. Caspase-3/-9 and PARP were activated, finally leading to the apoptosis of PC-3 cells. For the Pyridines androgen-sensitive (AR ) prostate cancer...
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Publisher
Elsevier
Copyright
Copyright © 2018 Elsevier Masson SAS
ISSN
0223-5234
eISSN
1768-3254
D.O.I.
10.1016/j.ejmech.2017.12.094
Publisher site
See Article on Publisher Site

Abstract

A series of new steroidal pyridines have been synthesized through the based-promoted three-component reaction and preliminarily evaluated for their antiproliferative activity against different types of cancer cell lines. SARs studies showed that the heterocyclic rings attached to the 4-position of the pyridine ring were preferred over the phenyl rings for the activity. Among these compounds, the most potent compound exhibited good growth inhibition against all the tested cancer cells, especially for PC-3 cells with an IC50 value of 1.55 μM. Further mechanistic studies revealed that the most potent compound inhibited colony formation, migration and evasion of PC-3 cells in a concentration-dependent manner as well as induced apoptosis of PC-3 cells possibly through the mitochondria-related apoptotic pathways. Caspase-3/-9 and PARP were activated, finally leading to the apoptosis of PC-3 cells. For the androgen-sensitive (AR+) prostate cancer cell line LNCaP, the most potent compound was less potent than abiraterone with the IC50 value of 8.48 and 3.29 μM, respectively. The most potent compound could be used as a starting point for the development of new steroidal heterocycles with improved anticancer potency and selectivity. The synthesized steroidal pyridines contain the functional -OEt and CN groups, which could be used for further modifications for the construction of the steroid library.

Journal

European Journal of Medicinal ChemistryElsevier

Published: Feb 10, 2018

References

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