title: Synthesis and biological evaluation of new phenothiazine derivatives bearing a pyrazole unit as protein farnesyltransferase inhibitors.
abstract: A new family of protein farnesyltransferase inhibitors, based on a phenothiazine scaffold, was designed and synthesized. The biological evaluation of these products showed that compounds 28 and 30 were the most active, with protein farnesyltransferase inhibition potencies in the low micromolar range. Compounds were also evaluated for their antiproliferative activity on a NCI-60 cancer cell line panel. Indenopyrazole 30 exhibited the most potent in vitro cytostatic activity inhibiting the growth of HCT-116, LOX IMVI and SK-MEL-5 cell lines.
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: Lavinia
authors.initials: L
authors.lastname: Baciu-Atudosie
authors.forename: Alina
authors.initials: A
authors.lastname: Ghinet
authors.forename: Amaury
authors.initials: A
authors.lastname: Farce
authors.forename: Joëlle
authors.initials: J
authors.lastname: Dubois
authors.forename: Dalila
authors.initials: D
authors.lastname: Belei
authors.forename: Elena
authors.initials: E
authors.lastname: Bîcu
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001665:Binding Sites; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D006801:Humans; D062105:Molecular Docking Simulation; D010640:Phenothiazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D010640:Phenothiazines; D011720:Pyrazoles; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase; C031637:phenothiazine