Abstract
In this paper we provide an overview of the status of various colchicine derivatives in preclinical development with special focus on their anti-cancer activity. We discuss several groups of compounds that have been designed to differentially bind with specific affinities for tubulin β isotypes, especially in regard to βIII, which is commonly over-expressed in cancer. Computational prediction, protein-based and cell-based assays are summarized as well as some animal tests conducted on these compounds. It is concluded that an untapped potential exists for exploiting the colchicine scaffold as a pharmacophore with the possibility of increasing its affinity for tubulin isotypes over-expressed in cancer and decreasing it for normal cells thereby widening the therapeutic window.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2538-2558 |
| Number of pages | 21 |
| Journal | Current Topics in Medicinal Chemistry |
| Volume | 17 |
| Issue number | 22 |
| DOIs | |
| State | Published - Sep 1 2017 |
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Keywords
- Animal tests
- Anti-cancer
- Colchicine Scaffold
- Pharmacophore
- Tubulin β isotypes
ASJC Scopus subject areas
- Drug Discovery
Cite this
Novel colchicine derivatives and their anti-cancer activity. / Johnson, Lorelei; Goping, Ing Swie; Rieger, Aja; Mane, Jonathan Y.; Huzil, Torin; Banerjee, Asok; Luduena, Richard; Hassani, Bashar; Winter, Philip; Tuszynski, Jack A.
In: Current Topics in Medicinal Chemistry, Vol. 17, No. 22, 01.09.2017, p. 2538-2558.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Novel colchicine derivatives and their anti-cancer activity
AU - Johnson, Lorelei
AU - Goping, Ing Swie
AU - Rieger, Aja
AU - Mane, Jonathan Y.
AU - Huzil, Torin
AU - Banerjee, Asok
AU - Luduena, Richard
AU - Hassani, Bashar
AU - Winter, Philip
AU - Tuszynski, Jack A.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - In this paper we provide an overview of the status of various colchicine derivatives in preclinical development with special focus on their anti-cancer activity. We discuss several groups of compounds that have been designed to differentially bind with specific affinities for tubulin β isotypes, especially in regard to βIII, which is commonly over-expressed in cancer. Computational prediction, protein-based and cell-based assays are summarized as well as some animal tests conducted on these compounds. It is concluded that an untapped potential exists for exploiting the colchicine scaffold as a pharmacophore with the possibility of increasing its affinity for tubulin isotypes over-expressed in cancer and decreasing it for normal cells thereby widening the therapeutic window.
AB - In this paper we provide an overview of the status of various colchicine derivatives in preclinical development with special focus on their anti-cancer activity. We discuss several groups of compounds that have been designed to differentially bind with specific affinities for tubulin β isotypes, especially in regard to βIII, which is commonly over-expressed in cancer. Computational prediction, protein-based and cell-based assays are summarized as well as some animal tests conducted on these compounds. It is concluded that an untapped potential exists for exploiting the colchicine scaffold as a pharmacophore with the possibility of increasing its affinity for tubulin isotypes over-expressed in cancer and decreasing it for normal cells thereby widening the therapeutic window.
KW - Animal tests
KW - Anti-cancer
KW - Colchicine Scaffold
KW - Pharmacophore
KW - Tubulin β isotypes
UR - http://www.scopus.com/inward/record.url?scp=85026458059&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85026458059&partnerID=8YFLogxK
U2 - 10.2174/1568026617666170104143618
DO - 10.2174/1568026617666170104143618
M3 - Review article
C2 - 28056740
AN - SCOPUS:85026458059
VL - 17
SP - 2538
EP - 2558
JO - Current Topics in Medicinal Chemistry
JF - Current Topics in Medicinal Chemistry
SN - 1568-0266
IS - 22
ER -