Novel Polycarbo-Substituted Alkyl (Thieno[3,2-c]quinoline)-2-Carboxylates: Synthesis and Cytotoxicity Studies

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.

Keywords

• 6,8-dibromo-4-chloroquinoline-3-carbaldehyde
• Suzuki-Miyaura cross-coupling
• alkyl thieno[3,2-c]quinoline-2-carboxylates
• MCF-7 cell line
• cytotoxicity