title: Synthesis and anticancer activity of analogues of phenstatin, with a phenothiazine A-ring, as a new class of microtubule-targeting agents.
abstract: A new family of microtubule-targeting agents with a phenothiazine A-ring was synthesized and evaluated for anti-proliferative activity and interaction with tubulin. These new derivatives showed significant activities against cellular proliferation and tubulin polymerization, rather similar to those of phenstatin. Phenothiazine derivative 21 proved to be the most potent compound synthesized with GI(50) values ranging from 29 to 93 nM on different cell lines. The same compound showed a better inhibition of COLO 205, A498, and MCF7 cell lines than the parent phenstatin.
authors.affiliation: Department of Organic Chemistry, Al. I. Cuza University of Iasi, Faculty of Chemistry, Bd. Carol I nr. 11, 700506 Iasi, Romania.
authors.forename: Cristina-Maria
authors.initials: CM
authors.lastname: Abuhaie
authors.forename: Elena
authors.initials: E
authors.lastname: Bîcu
authors.forename: Benoît
authors.initials: B
authors.lastname: Rigo
authors.forename: Philippe
authors.initials: P
authors.lastname: Gautret
authors.forename: Dalila
authors.initials: D
authors.lastname: Belei
authors.forename: Amaury
authors.initials: A
authors.lastname: Farce
authors.forename: Joëlle
authors.initials: J
authors.lastname: Dubois
authors.forename: Alina
authors.initials: A
authors.lastname: Ghinet
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D061986:MCF-7 Cells; D062105:Molecular Docking Simulation; D010640:Phenothiazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D058105:Polymerization / Q000187:drug effects; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry* / Q000378:metabolism; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D010640:Phenothiazines; D014404:Tubulin; D050257:Tubulin Modulators