An inexpensive, practical and one-pot method has been developed for the synthesis of quinoxalines fused with pyrano[3,4-b]indole, the central core of Lamellarin D. The methodology involved construction of the central pyranone ring via an AlCl₃-mediated heteroarylation-cyclization method. A number of compounds were prepared using this methodology, some of which were converted to the corresponding indol-3-ylquinoxaline derivatives. Several of the pyrano[3,4-b]indole fused quinoxalines showed promising growth inhibition of cervical and lung cancer cells and good interactions with topoisomerase I in silico.