Synthesis and in vitro antitumor evaluation of some new thiophenes and thieno[2,3-d]pyrimidine derivatives

Bioorg Chem. 2018 Dec:81:587-598. doi: 10.1016/j.bioorg.2018.09.022. Epub 2018 Sep 13.

Abstract

New thiophene (2-13) and thienopyrimidine (15-27) derivatives have been synthesized. Twenty three compounds were screened against five cell lines namely; hepatocellular carcinoma (liver) HepG-2, epidermoid carcinoma (larynx) Hep-2, mammary gland (breast) MCF-7, human prostate cancer PC-3 and epithelioid cervix carcinoma HeLa. The results revealed that compounds 15,16,17,24 and 25 showed the highest antitumor activity against all tested cell lines compared to Doxorubicin. In order to explain the expected mode of action of the observed anticancer activity, compounds 15,16,17,24 and 25 were selected to screen their DNA binding affinity and enzyme inhibitory activity against DNA polymerase, thymidylate synthase and tyrosine kinase. The results revealed that the tested compounds showed good DNA binding affinity as well as good inhibitory activity against the three enzymes which might explain the observed anticancer activity of the target compounds.

Keywords: Antitumor evaluation; Synthesis; Thienopyrimidines; Thiophenes.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Screening Assays, Antitumor
  • Humans
  • Neoplasms / drug therapy
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry*
  • Pyrimidines / pharmacology*
  • Thiophenes / chemical synthesis
  • Thiophenes / chemistry*
  • Thiophenes / pharmacology*

Substances

  • Antineoplastic Agents
  • Pyrimidines
  • Thiophenes
  • thienopyrimidine