title: Curcumin recognizes a unique binding site of tubulin.
abstract: Although curcumin is known for its anticarcinogenic properties, the exact mechanism of its action or the identity of the target receptor is not completely understood. Studies on a series of curcumin analogues, synthesized to investigate their tubulin binding affinities and tubulin self-assembly inhibition, showed that: (i) curcumin acts as a bifunctional ligand, (ii) analogues with substitution at the diketone and acetylation of the terminal phenolic groups of curcumin are less effective, (iii) a benzylidiene derivative, compound 7, is more effective than curcumin in inhibiting tubulin self-assembly. Cell-based studies also showed compound 7 to be more effective than curcumin. Using fluorescence spectroscopy we show that curcumin binds tubulin 32 Å away from the colchicine-binding site. Docking studies also suggests that the curcumin-binding site to be close to the vinblastine-binding site. Structure-activity studies suggest that the tridented nature of compound 7 is responsible for its higher affinity for tubulin compared to curcumin.
authors.affiliation: Department of Biochemistry, Bose Institute, Centenary Campus, P-1/12 CIT Scheme VIIM, Kolkata 700054, India.
authors.forename: Soumyananda
authors.initials: S
authors.lastname: Chakraborti
authors.forename: Lalita
authors.initials: L
authors.lastname: Das
authors.forename: Neha
authors.initials: N
authors.lastname: Kapoor
authors.forename: Amlan
authors.initials: A
authors.lastname: Das
authors.forename: Vishnu
authors.initials: V
authors.lastname: Dwivedi
authors.forename: Asim
authors.initials: A
authors.lastname: Poddar
authors.forename: Gopal
authors.initials: G
authors.lastname: Chakraborti
authors.forename: Mark
authors.initials: M
authors.lastname: Janik
authors.forename: Gautam
authors.initials: G
authors.lastname: Basu
authors.forename: Dulal
authors.initials: D
authors.lastname: Panda
authors.forename: Pinak
authors.initials: P
authors.lastname: Chakrabarti
authors.forename: Avadhesha
authors.initials: A
authors.lastname: Surolia
authors.forename: Bhabatarak
authors.initials: B
authors.lastname: Bhattacharyya
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000031:analogs & derivatives* / Q000378:metabolism*; D031541:Fluorescence Resonance Energy Transfer; D006358:Hot Temperature; D006801:Humans; D008870:Microtubules / Q000187:drug effects / Q000648:ultrastructure; D008938:Mitosis; D008958:Models, Molecular; D011485:Protein Binding; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D014404:Tubulin / Q000378:metabolism*; D050257:Tubulin Modulators / Q000378:metabolism*
chemical_list: D014404:Tubulin; D050257:Tubulin Modulators; D003474:Curcumin