title: Synthesis and cytotoxic activity of metallic complexes of lawsone.
abstract: In the present study, a series of metallic complexes of the 1,4-naphthoquinone lawsone (2-6) were synthesized and evaluated for potential cytotoxicity in a mouse leukemic macrophagic RAW 264.7 cell line. Cell viability was determined by the MTT assay. Significant growth inhibition was observed for the copper complex (4) with an IC(50) value of 2.5 μM. This compound was selected for further evaluation of cytotoxic activity on several human cancer cells including HT-29 (human colorectal adenocarcinoma), HepG2 (human hepatocellular carcinoma) and HeLa, (human cervical adenocarcinoma cells). Significant cell viability decrease was also observed in HepG2 cells. The apoptotic potential of this complex was evaluated in these cells. Compound 4 induced apoptosis by a mechanism that involves the activation of caspases 3, 8 and 9 and modulation of apoptotic-related proteins such as Bax, Bad, and p53. These results indicate that metal complexes of lawsone derivatives, in particular compound 4, might be used for the design of new antitumoral agents.
authors.affiliation: Instituto Universitario de Bio-Orgánica Antonio González, Departamento de Química Orgánica, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez 2, 38206 La Laguna, Tenerife, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Oramas-Royo
authors.forename: Concepción
authors.initials: C
authors.lastname: Torrejón
authors.forename: Irene
authors.initials: I
authors.lastname: Cuadrado
authors.forename: Rita
authors.initials: R
authors.lastname: Hernández-Molina
authors.forename: Sonsoles
authors.initials: S
authors.lastname: Hortelano
authors.forename: Ana
authors.initials: A
authors.lastname: Estévez-Braun
authors.forename: Beatriz
authors.initials: B
authors.lastname: de Las Heras
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D019073:HT29 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D008264:Macrophages / Q000187:drug effects; D008958:Models, Molecular; D015394:Molecular Structure; D009285:Naphthoquinones / Q000737:chemistry*; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D009285:Naphthoquinones; D009942:Organometallic Compounds; C005090:lawsone