Synthesis and structure–activity relationship of new cytotoxic agents targeting human glutathione-S-transferases

• Published in: European journal of medicinal chemistry Vol. 89; pp. 156 - 171
• Main Authors: Rotili, Dante, De Luca, Anastasia, Tarantino, Domenico, Pezzola, Silvia, Forgione, Mariantonietta, Morozzo della Rocca, Blasco, Falconi, Mattia, Mai, Antonello, Caccuri, Anna Maria
• Format: Journal Article
• Language: English
• Published: PARIS Elsevier Masson SAS 07.01.2015; Elsevier
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Cell Proliferation - drug effects; Chemistry, Medicinal; Dose-Response Relationship, Drug; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Glutathione S-Transferase pi - antagonists & inhibitors; Glutathione S-Transferase pi - metabolism; Glutathione-S-transferase; Humans; Imidazoles - chemical synthesis; Imidazoles - chemistry; Imidazoles - pharmacology; Life Sciences & Biomedicine; Models, Molecular; Molecular Structure; Naphthalenes - chemical synthesis; Naphthalenes - chemistry; Naphthalenes - pharmacology; Nitrobenzoxadiazole; Pharmacology & Pharmacy; Science & Technology; Sigma-complex; Structure-Activity Relationship; Suicide inhibitor; Water solubility; Water solubility; Nitrobenzoxadiazole; Suicide inhibitor; Sigma-complex; Glutathione-S-transferase; P1-1; APOPTOSIS; LIGAND-BINDING; MECHANISM; CELL-LINES; DRUGS; RESISTANCE; OSTEOSARCOMA; INHIBITORS; 6-(7-NITRO-2,1,3-BENZOXADIAZOL-4-YLTHIO)HEXANOL NBDHEX

The 6-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)thio)hexan-1-ol (NBDHEX, 1), a “suicide inhibitor” of the glutathione-S-transferase GSTP1-1, showed pro-apoptotic properties in tumor cells, but in vivo studies were limited by poor bioavailability and high affinity towards GSTM2-2, expressed in many non-...