title: Novel myricetin derivatives: Design, synthesis and anticancer activity.
abstract: Telomere and telomerase were closely related to occurrence and development of some cancers. To enhance ability of myricetin moiety for inhibiting telomerase, we designed a series of novel myricetin derivatives based on reasonable analysis. The telomerase inhibition assay showed that compound 6d displayed the most potent inhibitory activity with IC50 value of 0.91 μM. The anticancer activity assay showed that 6d exhibited high activity against human breast cells MDA-MB-231. The docking simulation of compound 6d was performed to get the probable binding model, the results demonstrated that the furan ring inserted into the active site deeply and had hydrophobic interactions with residues of Phe 568, Pro 627, four methoxy groups had hydrophobic interactions with residues of Phe 568, Pro 627, Lys 902, Val 904 and Pro 929. Western blot results showed that expression of p65 and TERT protein was clearly down-regulated by compound 6d. These data support further studies for the rational design of more efficient p65 and TERT modulators.
authors.affiliation: State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Guizhou University, Guiyang 55002, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xue
authors.affiliation: State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Guizhou University, Guiyang 55002, PR China. Electronic address: songbaoan22@yahoo.com.
authors.forename: Bao-An
authors.initials: BA
authors.lastname: Song
authors.affiliation: State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Guizhou University, Guiyang 55002, PR China.
authors.forename: Hong Ju
authors.initials: HJ
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei, 230032, PR China.
authors.forename: Xing Bao
authors.initials: XB
authors.lastname: Qi
authors.affiliation: Department of Bioscience, Bengbu Medical College, Bengbu, 233030, PR China.
authors.forename: Yin Jiu
authors.initials: YJ
authors.lastname: Huang
authors.affiliation: State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Guizhou University, Guiyang 55002, PR China; School of Pharmacy, Anhui Medical University, Hefei, 230032, PR China. Electronic address: xhliuhx@163.com.
authors.forename: Xin Hua
authors.initials: XH
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D015195:Drug Design; D005419:Flavonoids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; C040015:myricetin
keywords: Anticancer activity; Myricetin; Telomerase