title: Anti-proliferative activity of 2,6-dichloro-9- or 7-(ethoxycarbonylmethyl)-9H- or 7H-purines against several human solid tumour cell lines.
abstract: As leads we took several benzo-fused seven- and six-membered scaffolds linked to the pyrimidine or purine moieties with notable anti-proliferative activity against human breast, colon and melanoma cancerous cell lines. We then decided to maintain the double-ringed nitrogenous bases and change the other components to the ethyl acetate moiety. This way six purine and two 5-fluorouracil derivatives were obtained and evaluated against the MCF-7, HCT-116, A-375 and G-361 cancer cell lines. Two QSARs are obtained between the anti-proliferative IC₅₀ values for compounds 26-33 and the clog P against the melanoma cell lines A-375 and G-361. Our results show that two of the analogues [ethyl 2-(2,6-dichloro-9H- or 7H-purine-9- or 7-yl)acetates (30 and 33, respectively)] are potent cytotoxic agents against all the tumour cell lines assayed, showing single-digit micromolar IC₅₀ values. This exemplifies the potential of our previously reported purine compounds to qualify as lead structures for medicinal chemistry campaigns, affording simplified analogues easy to synthesize and with a noteworthy bioactivity. The selective activity of 30 and 33 against the melanoma cell line A-375, via apoptosis, supposes a great advantage for a future therapeutic use.
authors.affiliation: Departamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, Universidad de Granada, Campus de Cartuja s/n, 18071 Granada, Spain.
authors.forename: Fátima
authors.initials: F
authors.lastname: Morales
authors.affiliation: Instituto de Biopatología y Medicina Regenerativa (IBIMER), Departamento de Anatomía y Embriología Humana, Facultad de Medicina, Avenida de Madrid s/n, 18071 Granada, Spain; Departamento de Ciencias de la Salud, Facultad de Ciencias Experimentales y de la Salud, Paraje de las Lagunillas s/n, 23071 Jaén, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ramírez
authors.affiliation: Departamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, Universidad de Granada, Campus de Cartuja s/n, 18071 Granada, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Conejo-García
authors.affiliation: Instituto de Biopatología y Medicina Regenerativa (IBIMER), Departamento de Anatomía y Embriología Humana, Facultad de Medicina, Avenida de Madrid s/n, 18071 Granada, Spain.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Morata
authors.affiliation: Instituto de Biopatología y Medicina Regenerativa (IBIMER), Departamento de Anatomía y Embriología Humana, Facultad de Medicina, Avenida de Madrid s/n, 18071 Granada, Spain.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Marchal
authors.affiliation: Departamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, Universidad de Granada, Campus de Cartuja s/n, 18071 Granada, Spain. Electronic address: jmcampos@ugr.es.
authors.forename: Joaquín M
authors.initials: JM
authors.lastname: Campos
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D011687:Purines / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D011687:Purines
keywords: 5-Fluorouracil; Anti-tumour compounds; Apoptosis; Breast cancer; Colon cancer; Melanoma; Purines