Design, synthesis and antiproliferative activity of decarbonyl luotonin analogues

摘要

Abstract A small library of benzimidazole-fused pyrrolo[3,4- b ]quinoline has been synthesized from readily available benzimidazole 2-carbaldehyde and various substituted arylamines in good to excellent yields utilizing an intramolecular Povarov reaction catalyzed by boron trifluoride diethyl etharate as the key final step. The compounds thus synthesized can be considered as decarbonyl analogues of the anticancer alkaloid luotonin A and were evaluated in a DNA relaxation assay for their ability to inhibit human topoisomerase I. Interestingly, two of the compounds showed a remarkable activity that is comparable to that of the standard drug camptothecin. The compounds were also evaluated for their cytotoxic effect in four highly aggressive human cancer cell lines, namely KB, MDA-MB231 (breast), LNCap (prostate), and HT1080 (fibrosarcoma). Some of the compounds obtained showed promising cytotoxicities for these four cell lines. Graphical abstract Display Omitted Highlights ? A small library of novel D-ring modified luotonin analogues has been synthesized by intramolecular Povarov reactions. ? The synthesized compounds were evaluated in DNA relaxation assays for their ability to inhibit human topoisomerase I. ? The compounds were also evaluated for their cytotoxic effect in four highly aggressive human cancer cell lines.