Tubulin inhibitors targeting the colchicine binding site: a perspective of privileged structures
نویسندگان
چکیده
منابع مشابه
Novel Natural Product- and Privileged Scaffold-Based Tubulin Inhibitors Targeting the Colchicine Binding Site.
Tubulin inhibitors are effective anticancer agents, however, there are many limitations to the use of available tubulin inhibitors in the clinic, such as multidrug resistance, severe side-effects, and generally poor bioavailability. Thus, there is a constant need to search for novel tubulin inhibitors that can overcome these limitations. Natural product and privileged structures targeting tubul...
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To block the metabolically labile sites of novel tubulin inhibitors targeting the colchicine binding site based on SMART, ABI, and PAT templates, we have designed, synthesized, and biologically tested three focused sets of new derivatives with modifications at the carbonyl linker, the para-position in the C ring of SMART template, and modification of A ring of the PAT template. Structure-activi...
متن کاملOptimization of 4-(N-Cycloamino)phenylquinazolines as a Novel Class of Tubulin-Polymerization Inhibitors Targeting the Colchicine Site
The 6-methoxy-1,2,3,4-tetrahydroquinoline moiety in prior leads 2-chloro- and 2-methyl-4-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)quinazoline (1a and 1b) was modified to produce 4-(N-cycloamino)quinazolines (4a-c and 5a-m). The new compounds were evaluated in cytotoxicity and tubulin inhibition assays, resulting in the discovery of new tubulin-polymerization inhibitors. 7-Methoxy-4-(2-methylquin...
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Ample evidence has accumulated indicating that the information for forming microtubule lattice lies in the tubulin molecule. There are varieties of agents such as Mg2+ [l-3], dimethyl sulfoxide [4], polyethylene glycol, DEAE-dextran [S] and basic proteins [6-91 which could induce microtubule assembly in a purified preparation of tubulin. However, it appears that in those assembly conditions whe...
متن کاملPodophyllotoxin as a probe for the colchicine binding site of tubulin.
The binding of [3H]podophyllotoxin to tubulin, measured by a DEAE-cellulose filter paper method, occurs with an affinity constant of 1.8 X 10(6) M-1 (37 degrees at pH 6.7). Like colchicine, approximately 0.8 mol of podophyllotixin are bound per mol of tubulin dimer, and the reaction is entropy-driven (43 cal deg-1 mol-1). At 37 degrees the association rate constant for podophyllotoxin binding i...
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ژورنال
عنوان ژورنال: Future Medicinal Chemistry
سال: 2017
ISSN: 1756-8919,1756-8927
DOI: 10.4155/fmc-2017-0100