Novel polycarbo-substituted alkyl (thieno[3,2-c]quinoline)-2-carboxylates: synthesis and cytotoxicity studies

Molecules. 2014 Nov 13;19(11):18527-42. doi: 10.3390/molecules191118527.

Abstract

Direct one-pot base-promoted conjugate addition-elimination of 6,8-dibromo-4-chloroquinoline-3-carbaldehyde with methyl mercaptoacetate and subsequent cyclization afforded methyl [(6,8-dibromothieno[3,2-c]quinoline)]-2-carboxylate. The latter undergoes Suzuki-Miyaura cross-coupling with arylboronic acids to yield exclusively the corresponding alkyl [(6,8-diarylthieno[3,2-c]quinoline)]-2-carboxylates,. The cytotoxicity of the prepared compounds was evaluated against the human breast cancer cell line MCF-7 using the MTT assay. The effects of compounds 2, 3c and 4d on cell kinetics were further determined using the xCELLigence Real Time Cell Analysis (RTCA) system. In both the MTT assay and Real Time Cell Analysis, the compounds inhibited cancer cell growth in a dose- and time-dependent manner. Furthermore, on the basis of the calculated LC50 values, the compounds compared favourably with nocodazole, a well-established anticancer drug.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cytotoxins* / chemical synthesis
  • Cytotoxins* / chemistry
  • Cytotoxins* / pharmacology
  • Female
  • Heterocyclic Compounds, 3-Ring* / chemical synthesis
  • Heterocyclic Compounds, 3-Ring* / chemistry
  • Heterocyclic Compounds, 3-Ring* / pharmacology
  • Humans

Substances

  • Antineoplastic Agents
  • Cytotoxins
  • Heterocyclic Compounds, 3-Ring