Abstract
Malaria and cancer are deadly diseases affecting millions of people worldwide. Despite advances in research and treatment, these diseases continue to cause death worldwide. Although cancer and malaria's aetiology and clinical manifestations differ significantly, several commonalities have been discovered at the cellular and molecular levels. Both diseases include dysregulated cell growth and proliferation, with cancer defined by unregulated cell division and malaria by the Plasmodium parasite's rapid replication within red blood cells. Furthermore, cancer and malaria share signalling pathways and molecular targets contributing to disease progression. This suggests that there are similar biological pathways that therapeutic drugs could target. The linkage between malaria and cancer at a genetic level presents an intriguing connection. Several cancer-related genes and signalling pathways, such as the PI3K/AKT/mTOR pathway, have also been discovered to play critical roles in the Plasmodium parasite’s survival and proliferation within human hosts. This interaction suggests that drugs targeting specific molecular pathways in cancer may have therapeutic benefits on malaria and vice-versa.
The shared challenges of drug resistance in both cancer and malaria and the probable overlap in underlying cellular and molecular pathways drive the urgent need for novel drugs to address malaria and cancer. Through this study, we have synthesized several hybrid compounds: coumarin-triazole hybrids, coumarin-benzoxazine hybrids, isoxazole-triazole hybrids, benzoxazole-triazole hybrids, and benzoxazole-isoxazole hybrids. These compounds were characterized via 1H and 13C NMR Spectroscopy, HRMS, and FTIR. Their physicochemical properties were determined and rationalized for their cytotoxic activity against human embryonic kidney cells (HEK293 cells) and adenocarcinoma human epithelial cells (A549 cells). Compounds 224, 228a, and 231a exhibited the best cytotoxic effects against the A549 cell line (IC50 = 19.84 ± 1.19, 15.64 ± 0.21, and 14.46 ± 1.05 μg/mL) when compared to all the other hybrids that were evaluated for their cytotoxic activity. The investigation also showed that two compounds with the highest cytotoxicity against A549 cells possessed a phenyl group substituted with bromine at the ortho position.