Synthesis and Cytotoxicity of Substituted Ethyl 2‐Phenacyl‐3‐phenylpyrrole‐4‐carboxylates
- 16 June 2003
- journal article
- research article
- Published by Wiley in Archiv der Pharmazie
- Vol. 336 (3) , 181-190
- https://doi.org/10.1002/ardp.200390018
Abstract
The substituted ethyl-2-phenacyl-3-phenylpyrrole-4-carboxylates were synthesized by a condensation of a beta-chloroenal and an alpha-aminoketone under neutral conditions. They proved to be potent cytotoxic agents against the growth of murine L1210 and P388 leukemias and human HL-60 promyelocytic leukemia, HuT-78 lymphoma, and HeLa-S3 uterine carcinoma. Selective compounds were active against the growth of Tmolt3 and Tmolt4 leukemias and THP-1 acute monocytic leukemia, liver Hepe-2, ovary 1-A9, ileum HCT-8 adenocarcinoma, and osteosarcoma HSO. A mode of action study in HL-60 cells demonstrated that DNA and protein syntheses were inhibited after 60[TH]min at 100[TH]μM. DNA and RNA polymerases, PRPP-amido transferase, dihydrofolate reductase, thymidylate synthase, and TMP kinase activities were interfered with by the agent with reduction of d[NTP] pools. Nonspecific interaction with the bases of DNA and cross-linking of the DNA may play a role in the mode of action of these carboxylates.Keywords
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