Relationship between cytotoxicity and conversion of thiosangivamycin analogs to toyocamycin analogs in cell culture medium.

  title={Relationship between cytotoxicity and conversion of thiosangivamycin analogs to toyocamycin analogs in cell culture medium.},
  author={T. Renau and J. Lee and H. Kim and C. Young and L. Wotring and L. Townsend and J. Drach},
  journal={Biochemical pharmacology},
  volume={48 4},
Non-nucleoside analogs of the pyrrolopyrimidine nucleosides toyocamycin, sangivamycin and thiosangivamycin have been synthesized and their cytotoxicity in mammalian cells determined. While studying the effects of 5-thioamide-substituted analogs on cell growth, we observed an interesting phenomenon in which cells recovered spontaneously from growth inhibition during extended incubations. HPLC studies demonstrated that the 5-thioamide moiety of several structurally dissimilar 7-substituted 4… Expand
8 Citations
Synthesis and cytotoxicity of 4'-C- and 5'-C-substituted toyocamycins.
Toyocamycin and some analogues have shown potent antitumor activities; however, none of them could be used clinically primarily owing to their cytotoxicity to normal human cells. In order to overcomeExpand
Nonnucleoside Pyrrolopyrimidines with a Unique Mechanism of Action against Human Cytomegalovirus
The data indicate that these pyrrolopyrimidines target a viral protein that is required in an MOI-dependent manner and that is expressed early in the HCMV replication cycle. Expand
Derives antiviraux de pyrrolo(2,3-d)pyrimidine
L'invention concerne une nouvelle classe de pyrrolo[2,3-d]pyrimidines 4,5,6,7-substituees, non-nucleosidiques et non phosphorylatables, qui presentent a la fois des niveaux de cytotoxicite nettementExpand
A retrospective look at anthranilic diamide insecticides: discovery and lead optimization to chlorantraniliprole and cyantraniliprole.
A retrospective look is presented on the discovery of the class, along with chemistry highlights of the lead evolution to both products, which have excellent cross-spectrum activity against a range of insect orders, including both lepidopteran and hemipteran pests. Expand
Discovery of cyantraniliprole, a potent and selective anthranilic diamide ryanodine receptor activator with cross-spectrum insecticidal activity.
The chemistry, biology and structure-activity trends for a series of cyanoanthranilic diamides from which cyantraniliprole was selected for commercial development are reported on. Expand
An Improved Synthesis of the Versatile Heterocycle, 4-Amino-6-Bromo-5-Cyanopyrrolo[2,3-d]Pyrimidine
Abstract A fast and efficient method was developed for the preparation of 4-amino-6-bromo-5-cyanopyrrolo[2,3-d]pyrimidine from 2-amino-5-bromo-3,4-dicyanopyrrole, triethylorthoformate and ethanolicExpand
Plants that fight cancer
PART I: WHAT DO WE KNOW ABOUT CANCER AND ITS THERAPY? Incidence and Causes Classification of Cancer Types Therapy Conventional Cancer Treatments Advanced Cancer Treatments Other Advanced TherapiesExpand
The Therapeutic Targeting Of Folate Receptor Alpha Positive Tumors Via Folate Receptor Selective Novel 5- And 6- Substituted Pyrrolo [2,3-D]pyrimidine Antifolates"


Improved synthesis and biological evaluation of an acyclic thiosangivamycin active against human cytomegalovirus.
There is adequate separation between antiviral activity and cytotoxicity to merit further work with this class of pyrrolopyrimidines. Expand
Pyrrolo[2,3-d]pyrimidine nucleosides as inhibitors of human cytomegalovirus.
Seven arabinosyl and deoxyribosyl nucleosides appeared to act by inhibition of viral DNA synthesis as quantitated by DNA-DNA dot blot hybridization, and all compounds inhibited herpes simplex virus to a lesser extent than human cytomegalovirus. Expand
Comparison between the inhibitory activities of sangivamycin and thiosangivamycin on nuclear ribonucleic acid synthesis in L1210 cells in vitro.
It is suggested that sangivamycin and thiosangavamycin act as adenosine analogs to inhibit the transcription of all forms of nuclear RNA in L1210 cells. Expand
Flow cytometric evaluation of the cytotoxicity of novel antiviral compounds.
Two acyclic analogs of bromotubercidin were tested for cytotoxic effects on uninfected cells by monitoring cell growth and measuring cell cycle perturbations using flow cytometry, suggesting the two compounds acted by different biochemical mechanisms. Expand
Synthesis of Thio-AICA, 6-Thioxanthine, Isoguanine Analogs, and Their Ribosides
4-Amino-5-thiocarbamoylimidazole (II, thio-AICA) was prepared by direct thiation of 4-amino-5-imidazolecarboxamide (I, AICA) with phosphorus pentasulfide and also by addition of 4-amino-5-imidazoleExpand
Study of the cytotoxicity and metabolism of 4-amino-3-carboxamido-1-(beta-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidine using inhibitors of adenosine kinase and adenosine deaminase.
The greater in vivo antitumor activity of APPCR in comparison to the parent compound 4-amino-3-carboxamido-1-(beta-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidine may involve intrinsic differences in the effects of these two compounds on cells, as well as in their metabolisms. Expand
Pyrrolopyrimidine nucleosides. Part X. Synthesis of certain 4,5-disubstituted 7-(beta-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidines related to toyocamycin and sangivamycin.
Studies comparing the susceptibility towards nucleophilic attack of the 5-cyano-group of (10) with that of the 4-chloro-7-(β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine-5-carbonitrile indicate that under both basic and acidic conditions the cyano-function of ( 10) is the more reactive. Expand
Synthesis, cytotoxicity, and antiviral activity of some acyclic analogues of the pyrrolo[2,3-d]pyrimidine nucleoside antibiotics tubercidin, toyocamycin, and sangivamycin.
Evaluation of compounds 6, 7a, 7b, 7c, 9a, 9b, 9c, 11 for cytoxicity and activity against human cytomegalovirus (HCMV) and herpes simplex virus type 1 (HSV-1) revealed that only the carboxamide and the thioamide were active. Expand
Design, synthesis and activity against human cytomegalovirus of non-phosphorylatable analogs of toyocamycin, sangivamycin and thiosangivamycin
Abstract A number of 7-alkyl 4-aminopyrrolo[2,3- d pyrimidine derivatives related to toyocamycin, sangivamycin and thiosangivamycin have been prepared and tested for their activity against humanExpand
Pyrazolopyrimidine nucleosides. Part VII. The synthesis of certain pyrazolo [3,4‐d] pyrimidine nucleosides related to the nucleoside antibiotics toyocamycin and sangivamycin
The condensation of 4-acetamido-3-cyanopyrazolo[3,4-d]pyrimidine (5) with crystalline 2,3,5-tri-O-acetyl-β-D-ribofuranosyl chloride (6) has furnished a good yield of nucleoside material (7) which onExpand