Design and synthesis of novel EG5 inhibitors

M. Abualhasan, O. B. Sutcliffe, F. Kozielski, S. P. Mackay

Research output: Contribution to journalConference Contribution

Abstract

The currently available antimitotic drugs directly target the microtubule building blocks. These drugs induce adverse side-effects including neurotoxicity, and cancer cells can
potentially develop resistance to them. New antimitotic drugs act indirectly on microtubules, these drugs have specifi c functions on phases of mitosis, and their inhibition may produce fewer side-effects than tubulin drugs. Eg5 motors are a member of the kinesin family which are required for spindle bipolarity maintenance. Inhibition of these motors induces mono-asters cells. S-trityl-L-cysteine (STLC) is a specifi c and effective Eg5 inhibitor, the trityl group of the STLC binds to three hydrophobic sites inside the binding pocket [1]. Our aim is to design and synthesise high potency specific Eg5 inhibitors which have a higher inhibition activity than the STLC. Our suggested compounds have in general extended benzyl group, which is believed to be more fl exible compared to the phenyl group of the STLC. It is also believed that the
benzyl moiety will increase the hydrophobic binding to the Eg5 motors.
LanguageEnglish
Pages1367-1367
Number of pages1
JournalJournal of Pharmacy and Pharmacology
Volume62
Issue number10
Early online date3 Sep 2010
DOIs
Publication statusPublished - Oct 2010
EventUK-PharmSci 2010 – The Science of Medicines - Nottingham, United Kingdom
Duration: 1 Sep 20103 Sep 2010

Fingerprint

3-tritylthio-L-alanine
Antimitotic Agents
Microtubules
Kinesin
Tubulin
Drug-Related Side Effects and Adverse Reactions
Mitosis
Pharmaceutical Preparations
Binding Sites
Maintenance

Keywords

  • antimitotic drugs
  • side-effects
  • neurotoxicity
  • spindle bipolarity maintenance
  • Eg5 inhibitors
  • Eg5 motors

Cite this

Abualhasan, M. ; Sutcliffe, O. B. ; Kozielski, F. ; Mackay, S. P. / Design and synthesis of novel EG5 inhibitors. In: Journal of Pharmacy and Pharmacology. 2010 ; Vol. 62, No. 10. pp. 1367-1367.
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Design and synthesis of novel EG5 inhibitors. / Abualhasan, M.; Sutcliffe, O. B.; Kozielski, F.; Mackay, S. P.

In: Journal of Pharmacy and Pharmacology, Vol. 62, No. 10, 10.2010, p. 1367-1367.

Research output: Contribution to journalConference Contribution

TY - JOUR

T1 - Design and synthesis of novel EG5 inhibitors

AU - Abualhasan, M.

AU - Sutcliffe, O. B.

AU - Kozielski, F.

AU - Mackay, S. P.

PY - 2010/10

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N2 - The currently available antimitotic drugs directly target the microtubule building blocks. These drugs induce adverse side-effects including neurotoxicity, and cancer cells can potentially develop resistance to them. New antimitotic drugs act indirectly on microtubules, these drugs have specifi c functions on phases of mitosis, and their inhibition may produce fewer side-effects than tubulin drugs. Eg5 motors are a member of the kinesin family which are required for spindle bipolarity maintenance. Inhibition of these motors induces mono-asters cells. S-trityl-L-cysteine (STLC) is a specifi c and effective Eg5 inhibitor, the trityl group of the STLC binds to three hydrophobic sites inside the binding pocket [1]. Our aim is to design and synthesise high potency specific Eg5 inhibitors which have a higher inhibition activity than the STLC. Our suggested compounds have in general extended benzyl group, which is believed to be more fl exible compared to the phenyl group of the STLC. It is also believed that the benzyl moiety will increase the hydrophobic binding to the Eg5 motors.

AB - The currently available antimitotic drugs directly target the microtubule building blocks. These drugs induce adverse side-effects including neurotoxicity, and cancer cells can potentially develop resistance to them. New antimitotic drugs act indirectly on microtubules, these drugs have specifi c functions on phases of mitosis, and their inhibition may produce fewer side-effects than tubulin drugs. Eg5 motors are a member of the kinesin family which are required for spindle bipolarity maintenance. Inhibition of these motors induces mono-asters cells. S-trityl-L-cysteine (STLC) is a specifi c and effective Eg5 inhibitor, the trityl group of the STLC binds to three hydrophobic sites inside the binding pocket [1]. Our aim is to design and synthesise high potency specific Eg5 inhibitors which have a higher inhibition activity than the STLC. Our suggested compounds have in general extended benzyl group, which is believed to be more fl exible compared to the phenyl group of the STLC. It is also believed that the benzyl moiety will increase the hydrophobic binding to the Eg5 motors.

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KW - side-effects

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M3 - Conference Contribution

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