title: Synthesis and biological evaluation of 5,10-dihydro-11H-dibenzo[b,e][1,4]diazepin-11-one structural derivatives as anti-cancer and apoptosis inducing agents.
abstract: A series of thirteen 5H-dibenzo [b,e][1,4]diazepin-11(10H)-one structural derivatives has been synthesized and evaluated for anti-proliferative activity against five human cancer cell lines. Compound 9a exhibited potent tumour growth inhibition in all cell lines with IC50 values in the range of 0.71-7.29 μM. Experiments on lung (A549) and breast (MDAMB-231) cancer cell lines to investigate the mechanisms of growth inhibition and apoptosis inducing effects of 9a showed that it arrested both cancer cell lines in the G2/M phase of cell cycle in a dose dependent manner. Hoechst staining analysis revealed that 9a inhibited tumour cell proliferation through apoptosis induction. Additionally, the mitochondrial membrane potential (ΔΨm) was affected and the levels of reactive oxygen species (ROS) were raised. The simple synthetic preparation and their biological properties make these dibenzodiazepinone-triazole scaffolds promising new entities for the development of cancer therapeutics.
authors.affiliation: School of Applied Sciences, RMIT University, Melbourne 3001, Australia; IICT-RMIT Research Centre SIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India; Division of Natural Products Chemistry, CSIR-IICT, Hyderabad 500 007, India.
authors.forename: Chintakunta
authors.initials: C
authors.lastname: Praveen Kumar
authors.affiliation: School of Applied Sciences, RMIT University, Melbourne 3001, Australia; Health Innovations Research Institute, RMIT University, Melbourne 3083, Australia; Ian Potter NanoBioSensing Facility, NanoBiotechnology Research Laboratory, School of Applied Sciences, RMIT University, Melbourne 3000, Australia; Centre for Advanced Materials and Industrial Chemistry, RMIT University, Melbourne 3000, Australia.
authors.forename: T Srinivasa
authors.initials: TS
authors.lastname: Reddy
authors.affiliation: Division of Natural Products Chemistry, CSIR-IICT, Hyderabad 500 007, India.
authors.forename: Prathama S
authors.initials: PS
authors.lastname: Mainkar
authors.affiliation: School of Applied Sciences, RMIT University, Melbourne 3001, Australia; Health Innovations Research Institute, RMIT University, Melbourne 3083, Australia; Ian Potter NanoBioSensing Facility, NanoBiotechnology Research Laboratory, School of Applied Sciences, RMIT University, Melbourne 3000, Australia.
authors.forename: Vipul
authors.initials: V
authors.lastname: Bansal
authors.affiliation: School of Applied Sciences, RMIT University, Melbourne 3001, Australia; Health Innovations Research Institute, RMIT University, Melbourne 3083, Australia; Ian Potter NanoBioSensing Facility, NanoBiotechnology Research Laboratory, School of Applied Sciences, RMIT University, Melbourne 3000, Australia; Centre for Advanced Materials and Industrial Chemistry, RMIT University, Melbourne 3000, Australia.
authors.forename: Ravi
authors.initials: R
authors.lastname: Shukla
authors.affiliation: Division of Natural Products Chemistry, CSIR-IICT, Hyderabad 500 007, India. Electronic address: srivaric@iict.res.in.
authors.forename: Srivari
authors.initials: S
authors.lastname: Chandrasekhar
authors.affiliation: School of Applied Sciences, RMIT University, Melbourne 3001, Australia. Electronic address: helmut.hugel@rmit.edu.au.
authors.forename: Helmut M
authors.initials: HM
authors.lastname: Hügel
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001381:Azepines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: C000611549:5,10-dihydro-11H-dibenzo(b,e)(1,4)diazepin-11-one; D000970:Antineoplastic Agents; D001381:Azepines; D017382:Reactive Oxygen Species
keywords: Anti-cancer activity; Apoptosis; Dibenzodiazepinones; Triazoles