title: Design and synthesis of pyrido[3,2-α]carbazole derivatives and their analogues as potent antitumour agents.
abstract: A series of pyrido[3,2-α]carbazole derivatives and their analogues have been prepared and evaluated for their antitumour activity against human lung cancer A549 cells and colon cancer HT29 cells. The intermediates 4a-4k are successfully synthesized from 1a-1k and ethyl 2-(3-bromopyridin-2-yl)acetate by Knoevenagel condensation and intramolecular Heck-type reaction, and this is a novel and efficient synthetic approach to the core scaffold of the target compounds. These target compounds have shown an interesting antitumour profile towards the tested cell lines with IC50 values ranging from 0.07 μM to 4.45 μM. Among all the compounds synthesized, 8 compounds show higher potency than R16, 12 compounds are as potent as R16, and 6 compounds are less potent than R16. The best compound 24 is 7 times and approximately 10 times as potent as R16 against A549 and HT29 cells, respectively.
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemical Engineering, Wuhan University of Technology, 205 Luo Shi Road, Wuhan, Hubei 430070, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.forename: Zhi-Zhou
authors.initials: ZZ
authors.lastname: Yue
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Feng
authors.forename: Qian
authors.initials: Q
authors.lastname: He
authors.forename: Ze-Hong
authors.initials: ZH
authors.lastname: Miao
authors.forename: Chun-Hao
authors.initials: CH
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002227:Carbazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D019073:HT29 Cells; D006801:Humans; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D053644:Naphthalimides / Q000737:chemistry; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012995:Solubility
chemical_list: D000970:Antineoplastic Agents; D002227:Carbazoles; D053644:Naphthalimides; D011725:Pyridines; C586656:pyrido(3,2-alpha)carbazole; C041514:carbazole
keywords: Analogues; Antitumour profile; Potency; Pyrido[3,2-α]carbazole; Synthetic approach