Title

Synthesis And Cytotoxicity Of 2,4-Disubstituted And 2,3,4-Trisubstituted Brominated Pyrroles In Murine And Human Cultured Tumor Cells

Keywords

Brominated pyrroles; DNA cross-linking; Purine synthesis inhibitors

Abstract

The 2,4-disubstituted and 2,3,4-trisubstituted brominated pyrroles were successfully prepared and demonstrated potent cytotoxicity against the growth of suspended murine and human tumors, i.e. leukemia and lymphomas, acute monocytic leukemia, and HeLa-S3 uterine carcinoma. The brominated compounds were more selective in inhibiting the growth of tumors derived from human solid tumors. Nevertheless, activity with some of the derivatives occurred in the human KB nasopharynx, SW-480 colon, and HCT ileum adenocarcinoma, and lung A549 carcinoma screens. In Tmolt4 T cell leukemia cells DNA synthesis was reduced over 60 min from 25 to 100 μM followed by RNA synthesis reduction. De novo purine synthesis was retarded with the regulatory enzyme PRPP-amido transferase being markedly inhibited with less effects on the activities of IMP dehydrogenase, dihydrofolate reductase, and the nucleoside kinases. After 60 min incubations d[TTP] and d[GTP] pools were marginally reduced. In vitro ct-DNA studies suggest that the agents may affect the DNA molecule itself with increased DNA viscosity and the Tmolt4 studies suggest that DNA cross-linking of DNA strands may be present.

Publication Date

1-1-2000

Publication Title

Archiv der Pharmazie

Volume

333

Issue

1

Number of Pages

3-9

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1002/(SICI)1521-4184(200001)333:1<3::AID-ARDP3>3.0.CO;2-4

Socpus ID

0033985201 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/0033985201

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