Novel polycarbo-substituted alkyl (thieno[3,2-c]quinoline)-2-carboxylates: synthesis and cytotoxicity studies.
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.
Department of Chemistry, College of Science, Engineering and Technology, University of South Africa, P.O. Box 392, Pretoria 0003, South Africa. mphahmj@unisa.ac.za.
Malose Jack
MJ
Mphahlele
Department of Chemistry, College of Science, Engineering and Technology, University of South Africa, P.O. Box 392, Pretoria 0003, South Africa. malulmm@unisa.ac.za.
Marole Maria
MM
Maluleka
Department of Life and Consumer Sciences, College of Agriculture and Environmental Sciences, University of South Africa, Private Bag X06, Florida 1710, South Africa. makhat@unisa.ac.za.
Tshepiso Jan
TJ
Makhafola
Department of Anatomy and Physiology, University of Pretoria, P/Bag X04, Pretoria 0110, South Africa. peace.mabeta@up.ac.za.
Peace
P
Mabeta
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D003603:Cytotoxins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans
D000970:Antineoplastic Agents; D003603:Cytotoxins; D006575:Heterocyclic Compounds, 3-Ring