title: Design, Synthesis and Molecular Docking Studies of Novel Indole-Pyrimidine Hybrids as Tubulin Polymerization Inhibitors.
abstract: A series of novel hybrids of indole-pyrimidine-containing piperazine moiety were designed, synthesized and evaluated for their antiproliferative and tubulin polymerization inhibitory activities. The results indicated that most of these compounds possessed significant cytotoxic potency against four cancer cell lines, HT-29, A549, MDA-MB-231 and MCF-7. Particularly, the most promising compound 34 showed more potent and broad-spectrum cytotoxic activities with the IC50 values ranged from 5.01 to 14.36 μm against A549, MDA-MB-231 and MCF-7 cell lines. Meanwhile, 34 also displayed the most potent tubulin polymerization inhibitory activity with IC50 value of 11.2 μm. Furthermore, molecular docking analysis demonstrated 34 interacts and binds efficiently with the tubulin protein at the colchicine-binding site. It was worth noting that the compound did not affect the normal human embryonic kidney cells, HEK-293. These results suggest that this novel class of indole-pyrimidine hybrids may have potential to be developed as new a class of tubulin polymerization inhibitors.
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Meng-Jin
authors.initials: MJ
authors.lastname: Hu
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Hai-Kui
authors.initials: HK
authors.lastname: Yang
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Yu-Rong
authors.initials: YR
authors.lastname: Chen
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Tian-Zhu
authors.initials: TZ
authors.lastname: Ma
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Lu
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Wen-Wei
authors.initials: WW
authors.lastname: You
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Pei-Liang
authors.initials: PL
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D019073:HT29 Cells; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D061986:MCF-7 Cells; D062105:Molecular Docking Simulation; D055503:Protein Multimerization / Q000187:drug effects; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013552:Swine; D014404:Tubulin / Q000737:chemistry / Q000187:drug effects; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011743:Pyrimidines; D014404:Tubulin; D050257:Tubulin Modulators
keywords: antiproliferative activity; indole; pyrimidine; tubulin polymerization inhibitor