title: Antimitotic activity of the pyrimidinone derivative py-09 on sea urchin embryonic development.
abstract: Chemotherapy is the main cancer treatment and consists of drug administration that interferes with several metabolic pathways, leading to tumor cell death. Antimitotic drugs have a relevant role in chemotherapy. This study aimed to investigate the effect of a pyrimidinone derivative (6-(p-Anisyl)-2-(p-chlorophenyl)-4-oxo-3,4-dihydropyrimidine-5-carbonitrile, Py-09) on sea urchin embryonic development model. The effects of the compound were analyzed on fertilization, embryonic development, mitochondrial membrane potential (ΔΨm), production of reactive oxygen species (ROS) and ABC transporter activity. Py-09 inhibited the fertilization and the embryonic development in a time and dose-dependent pattern, with the maximum effect at 50 μM (EC50=12.5 μM). Py-09 induced the loss of ΔΨm without altering ROS intracellular levels. Morphological changes were observed in the pattern of embryo cleavage (unequal cleavage) and at larval stages (fissures of spicules and pigment cell leakage). We also demonstrated that Py-09 is not an ABC transporter substrate and the derivative does not circumvent the MXR phenomenon. Our study reports--for the first time--the antimitotic activity of Py-09 and stimulates new research on the potential of Py-09 as a pharmacological tool for in vitro studies, as well as its use as a new anticancer drug.
authors.affiliation: Laboratório de Biologia Celular e do Desenvolvimento (LABID), Departamento de Biologia Molecular, Universidade Federal da Paraíba, João Pessoa, Paraíba, Brazil.
authors.forename: Dalliane
authors.initials: D
authors.lastname: Macedo
authors.affiliation: Departamento de Farmácia, Universidade Estadual da Paraíba, Campina Grande, Paraíba, Brazil.
authors.forename: Francisco Jaime Bezerra
authors.initials: FJ
authors.lastname: Mendonça Júnior
authors.affiliation: Departamento de Farmácia, Universidade Estadual da Paraíba, Campina Grande, Paraíba, Brazil.
authors.forename: Ricardo Olimpio
authors.initials: RO
authors.lastname: de Moura
authors.affiliation: Laboratório de Biologia Celular e do Desenvolvimento (LABID), Departamento de Biologia Molecular, Universidade Federal da Paraíba, João Pessoa, Paraíba, Brazil. Electronic address: marques@ltf.ufpb.br.
authors.forename: Luis Fernando
authors.initials: LF
authors.lastname: Marques-Santos
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D050256:Antimitotic Agents / Q000494:pharmacology*; D004625:Embryo, Nonmammalian / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects; D005260:Female; D005306:Fertilization / Q000187:drug effects; D005452:Fluoresceins / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D011744:Pyrimidinones / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012617:Sea Urchins
chemical_list: C000611399:(6-(p-anisyl)-2-(p-chlorophenyl)-4-oxo-3,4-dihydropyrimidine-5-carbonitrile; D018528:ATP-Binding Cassette Transporters; D050256:Antimitotic Agents; D005452:Fluoresceins; D011744:Pyrimidinones; D017382:Reactive Oxygen Species; C007740:fluorexon
keywords: Antimitotic; Antiproliferative; Embryonic development; Embryotoxicity; Pyrimidinone derivative; Sea urchin