title: Synthesis, biological evaluation and molecular docking studies of trans-indole-3-acrylamide derivatives, a new class of tubulin polymerization inhibitors.
abstract: In this study, we synthesized a series of trans-indole-3-acrylamide derivatives (3a-k) and investigated their activity for inhibition of cell proliferation against five human cancer cell lines (HeLa, MCF7, MDA-MB-231, Raji and HL-60) by MTT assay. Compound 3e showed significant antiproliferative activity against both the Raji and HL-60 cell lines with IC50 values of 9.5 and 5.1 μM, respectively. Compound 3e also exhibited moderate inhibitory activity on tubulin polymerization (IC50=17 μM). Flow cytometric analysis of cultured cells treated with 3e also demonstrated that the compound caused cell cycle arrest at the G2/M phase in HL-60 and HeLa cells. Moreover, 3e, the most active compound, caused an apoptotic cell death through the activation of caspase-3. Docking simulations suggested that 3e binds to the colchicine site of tubulin.
authors.affiliation: Division of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, 06330 Etiler, Ankara, Turkey. Electronic address: baytas@gazi.edu.tr.
authors.forename: Sultan Nacak
authors.initials: SN
authors.lastname: Baytas
authors.affiliation: Division of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, 06330 Etiler, Ankara, Turkey.
authors.forename: Nazan
authors.initials: N
authors.lastname: Inceler
authors.affiliation: Department of Medical Biology and Genetics, Faculty of Medicine, Gazi University, 06500 Besevler, Ankara, Turkey.
authors.forename: Akin
authors.initials: A
authors.lastname: Yilmaz
authors.affiliation: Division of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, 06330 Etiler, Ankara, Turkey.
authors.forename: Abdurrahman
authors.initials: A
authors.lastname: Olgac
authors.affiliation: Department of Medical Biology and Genetics, Faculty of Medicine, Gazi University, 06500 Besevler, Ankara, Turkey.
authors.forename: Sevda
authors.initials: S
authors.lastname: Menevse
authors.affiliation: Division of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, 06330 Etiler, Ankara, Turkey.
authors.forename: Erden
authors.initials: E
authors.lastname: Banoglu
authors.affiliation: Screening Technologies Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, United States.
authors.forename: Ernest
authors.initials: E
authors.lastname: Hamel
authors.affiliation: Department of Women's and Children's Health, Laboratory of Oncohematology, University of Padova, 35128 Padova, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Bortolozzi
authors.affiliation: Department of Women's and Children's Health, Laboratory of Oncohematology, University of Padova, 35128 Padova, Italy.
authors.forename: Giampietro
authors.initials: G
authors.lastname: Viola
mesh_terms: D020106:Acrylamide / Q000737:chemistry*; D000178:Acrylamides / Q000737:chemistry* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D055503:Protein Multimerization / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry* / Q000378:metabolism; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: C000600993:(E)-3-(1H-Indol-3-yl)-N-(2,4,6-trimethoxyphenyl)acrylamide; D000178:Acrylamides; D000970:Antineoplastic Agents; D007211:Indoles; D014404:Tubulin; D050257:Tubulin Modulators; D020106:Acrylamide; D053148:Caspase 3
keywords: Anticancer activity; Apoptosis; Cell cycle arrest; Colchicine binding; Indole; Molecular docking; Synthesis; Tubulin polymerization