Design, synthesis and biological evaluation of new naphtalene diimides bearing isothiocyanate functionality.
The synthesis and the biological activities of new derivatives 1-3, characterized by the isothiocyanate (ITC) functionalities coming from sulforaphane (SFN), a well-known anticancer natural product, were reported. The most interesting compound of the series was 2. It was chemically characterized by two ITC functionalities mounted on the 1,4,5,8-naphthalentetracarboxylic diimide (NDI) scaffold through two polymethylene chains, each constituted by three carbon units. It demonstrated an IC(50) value in the submicromolar range, more potent than SFN, displaying also the ability to trigger apoptotic induction in the same range by eliciting both extrinsic and intrinsic apoptotic pathways. Finally, it was observed that 2 inhibited the cell growth by blocking the cell cycle in G1 phase.
Dipartimento di Scienze Farmaceutiche, Alma Mater Studiorum, Università di Bologna, Via Belmeloro 6, 40126 Bologna, Italy. anna.minarini@unibo.it
Anna
A
Minarini
Andrea
A
Milelli
Vincenzo
V
Tumiatti
Lorenzo
L
Ferruzzi
Melinda-Rita
MR
Marton
Eleonora
E
Turrini
Patrizia
P
Hrelia
Carmela
C
Fimognari
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D017879:Isothiocyanates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D019169:Jurkat Cells; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization
D000970:Antineoplastic Agents; D017879:Isothiocyanates; D009281:Naphthalenes