title: Synthesis of aryl-substituted naphthalene-linked pyrrolobenzodiazepine conjugates as potential anticancer agents with apoptosis-inducing ability.
abstract: A library of new aryl-substituted naphthalene C8-linked pyrrolo[2,1-c][1,4]benzodiazepine (PBD) conjugates with various linker architectures were designed, synthesized, and evaluated for their anticancer activity against a panel of 11 human cancer cell lines. All 32 conjugates show anticancer potential, with some of them exhibiting particularly high activity (0.01-0.19 μM). Thermal denaturation studies showed effective DNA binding capacity relative to DC-81. In assays for biological activity relating to cell-cycle distribution, these PBD conjugates induce G₀/G₁-phase arrest and also cause an increase in the levels of p53 and caspase-9 proteins, followed by apoptotic cell death. One conjugate in particular is the most promising candidate of the series, with the potential to be selected for further studies, either alone or in combination with existing anticancer therapies.
authors: Chemical Biology Laboratory, Indian Institute of Chemical Technology, Hyderabad 500607, India. ahmedkamal@iict.res.in
authors: Ahmed
authors: A
authors: Kamal
authors: M Kashi
authors: MK
authors: Reddy
authors: M Janaki
authors: MJ
authors: Ramaiah
authors: Y V V
authors: YV
authors: Srikanth
authors: Rajender
authors: V Santosh
authors: VS
authors: Reddy
authors: G Bharath
authors: GB
authors: Kumar
authors: S N C V L
authors: SN
authors: Pushpavalli
authors: Indira
authors: I
authors: Bag
authors: Aarti
authors: A
authors: Juvekar
authors: Subrata
authors: S
authors: Sen
authors: Surekha M
authors: SM
authors: Zingde
authors: Manika
authors: M
authors: Pal-Bhadra
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001569:Benzodiazepines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D015195:Drug Design; D006801:Humans; D009281:Naphthalenes / Q000737:chemistry / Q000494:pharmacology*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D009281:Naphthalenes; D011758:Pyrroles; D016159:Tumor Suppressor Protein p53; C438462:pyrrolo(2,1-c)(1,4)benzodiazepine; D001569:Benzodiazepines; C031721:naphthalene; D053453:Caspase 9