title: The cytotoxic activity of 1-acyl- and 1,2-diacyl-4,4-diethyl-3,5-pyrazolidinediones.
abstract: The 1-acyl- and 1,2-diacyl-4,4-diethyl-3,5-pyrazolinediones proved to be cytotoxic against the growth of a number of cell lines, including murine and human leukemias. HeLa suspended carcinoma, colon adencarcinoma SW480, KB nasopharynx and glioma tumors. Selected compounds were also active in the human lung bronchogenic MB-9812, and osteosarcoma TE418 screens. These derivatives were active in vivo in the Ehrlich ascites carcinoma screen in CF-1 mice at 8 mg/kg/day I.P. The mode of action in Tmol3 leukemia cells showed that the compounds reduced de novo synthesis of purines and pyrimidines and inhibited dihydrofolate reductase and ribonucleoside reductase activities. The DNA molecule was not a target although limited DNA strand scission may be possible.
authors.affiliation: Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27599-7360, USA.
authors.forename: I H
authors.initials: IH
authors.lastname: Hall
authors.forename: R A
authors.initials: RA
authors.lastname: Izydore
authors.forename: T S
authors.initials: TS
authors.lastname: Vital
authors.forename: S Y
authors.initials: SY
authors.lastname: Chen
authors.forename: M C
authors.initials: MC
authors.lastname: Miller
authors.forename: J A
authors.initials: JA
authors.lastname: Bernal-Ramirez
authors.forename: W A
authors.initials: WA
authors.lastname: Okwisa
authors.forename: K G
authors.initials: KG
authors.lastname: Rajendran
mesh_terms: D000230:Adenocarcinoma; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use* / Q000633:toxicity*; D001932:Brain Neoplasms; D002283:Carcinoma, Bronchogenic; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy*; D003110:Colonic Neoplasms; D004249:DNA Damage; D004354:Drug Screening Assays, Antitumor; D005493:Folic Acid Antagonists; D005910:Glioma; D006801:Humans; D007624:KB Cells; D007938:Leukemia; D007942:Leukemia, Experimental; D008175:Lung Neoplasms; D051379:Mice; D008815:Mice, Inbred Strains; D012516:Osteosarcoma; D011687:Purines / Q000378:metabolism; D011720:Pyrazoles / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity*; D011743:Pyrimidines / Q000378:metabolism; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors; D012878:Skin Neoplasms; D013329:Structure-Activity Relationship; D014410:Tumor Stem Cell Assay
chemical_list: D000970:Antineoplastic Agents; D005493:Folic Acid Antagonists; D011687:Purines; D011720:Pyrazoles; D011743:Pyrimidines; D012264:Ribonucleotide Reductases