In vitro cytotoxic activity evaluation of phenytoin derivatives against human leukemia cells. 2016

Katarzyna Śladowska, and Jadwiga Handzlik, and Katarzyna Kieć-Kononowicz, and Lidia Mazur

Hydantoin derivatives, including phenytoin (5,5-diphenylhydantoin), have recently gained attention as they possess a variety of important biochemical and pharmacological properties. Nevertheless, available information on anticancer activity of hydantoin derivatives is still scarce. Here, we evaluated possible antileukemic potential of four phenytoin analogs, namely: methyl 2-(2,4-dioxo-5,5-diphenylimidazolidin-3-yl)propanoate (1), methyl 2-(1-(3-bromopropyl)-2,4-dioxo-5,5-diphenylimidazolidin-3-yl)propanoate (2), 1-(3-bromopropyl)-3-methyl-5,5-diphenylimidazolidine-2,4-dione (3) and 1-(3-bromobutyl)-3-methyl-5,5-diphenylimidazolidine-2,4-dione (4). The experiments were performed on human acute histiocytic lymphoma U937 cells and human promyelocytic leukemia HL-60 cells. The present study was conducted using spectrophotometric 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay and the electronic Beckman-Coulter method. We observed temporary changes in the leukemia cell viability, volume and count. The effects of the four 5,5-diphenylhydantoin derivatives on U937 and HL-60 cells depended on the agent tested and its concentration, the time intervals after the compound application, and the leukemia cell line used. HL-60 cells were more sensitive than U937 cells to the action of the phenytoin analogs (1-4). The antileukemic activities of the three bromoalkyl diphenylhydantoin derivatives (2, 3, and 4) were stronger than that of the compound 1 [methyl 2-(2,4-dioxo-5,5-diphenylimidazolidin-3-yl) propanoate], with no bromoalkyl substituent. The structural modifications of 5,5-diphenylhydantoin are responsible for such varied antileukemic potential of its four derivatives.

UI MeSH Term Description Entries
D007938 Leukemia A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006) Leucocythaemia,Leucocythemia,Leucocythaemias,Leucocythemias,Leukemias
D010672 Phenytoin An anticonvulsant that is used to treat a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. Diphenylhydantoin,Fenitoin,Phenhydan,5,5-Diphenylhydantoin,5,5-diphenylimidazolidine-2,4-dione,Antisacer,Difenin,Dihydan,Dilantin,Epamin,Epanutin,Hydantol,Phenytoin Sodium,Sodium Diphenylhydantoinate,Diphenylhydantoinate, Sodium
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D018922 HL-60 Cells A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8) HL60 Cells,Cell, HL60,Cells, HL60,HL 60 Cells,HL-60 Cell,HL60 Cell
D020298 U937 Cells A human cell line established from a diffuse histiocytic lymphoma (HISTIOCYTIC LYMPHOMA, DIFFUSE) and displaying many monocytic characteristics. It serves as an in vitro model for MONOCYTE and MACROPHAGE differentiation. Cell, U937,Cells, U937,U937 Cell

Related Publications

Katarzyna Śladowska, and Jadwiga Handzlik, and Katarzyna Kieć-Kononowicz, and Lidia Mazur
March 2021, Molecular biology reports,
Katarzyna Śladowska, and Jadwiga Handzlik, and Katarzyna Kieć-Kononowicz, and Lidia Mazur
August 2009, Investigational new drugs,
Katarzyna Śladowska, and Jadwiga Handzlik, and Katarzyna Kieć-Kononowicz, and Lidia Mazur
June 2009, Acta pharmaceutica (Zagreb, Croatia),
Katarzyna Śladowska, and Jadwiga Handzlik, and Katarzyna Kieć-Kononowicz, and Lidia Mazur
March 2018, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie,
Katarzyna Śladowska, and Jadwiga Handzlik, and Katarzyna Kieć-Kononowicz, and Lidia Mazur
September 2023, BMC complementary medicine and therapies,
Katarzyna Śladowska, and Jadwiga Handzlik, and Katarzyna Kieć-Kononowicz, and Lidia Mazur
July 2017, Bioorganic & medicinal chemistry,
Katarzyna Śladowska, and Jadwiga Handzlik, and Katarzyna Kieć-Kononowicz, and Lidia Mazur
January 2018, Anti-cancer agents in medicinal chemistry,
Katarzyna Śladowska, and Jadwiga Handzlik, and Katarzyna Kieć-Kononowicz, and Lidia Mazur
May 2007, Chemistry & biodiversity,
Katarzyna Śladowska, and Jadwiga Handzlik, and Katarzyna Kieć-Kononowicz, and Lidia Mazur
November 2023, International journal of molecular sciences,
Katarzyna Śladowska, and Jadwiga Handzlik, and Katarzyna Kieć-Kononowicz, and Lidia Mazur
November 2022, Seminars in cancer biology,
Copied contents to your clipboard!