Novel Coumarin-Indole Hybrids as Cytotoxic Candidates: Synthesis and Antiproliferative Activity

Abstract

Cancer is regarded as a nightmare for humanity and a challenging task for medical professionals. Twelve hydrides (2a-2l), made of trifunctionalized coumarin and various substituted indoles, were created in an effort to realize the hope of a cancer cure. The 4,5-dimethoxysalicylaldehyde and ethyl acetoacetate were combined in a Knoevenagel reaction to create the coumarin component. The construction of the indole component involved converting various aminoindoles through diazotization and Sandmeyer reactions to twelve substituted indoles (1a-1l). These two components were combined through a Michael addition reaction to create the desired hybrids. Investigating their spectra released from various spectroscopical instruments allowed researchers to determine the 2D molecular frameworks of these hybrids. Studying the survival of nine tumor cell types after treatment with the synthesized hybrids enabled researchers to estimate there in vitro impact as cytotoxic candidates. By checking the cell viability using an MTT marker, it was possible to see that this effect was antiproliferative. The cytotoxicity measurements, IC50 scores, revealed a number of intriguing facts. To start, the synthetic hybrids displayed a relatively similar cytotoxic pattern against the cancerous cell lines under investigation. Second, compared to hybrids with chloride, hydroxyl, or methoxy substituents, fluorinated hybrids are more toxic to cancerous cells. Finally, hybrids with indole substituted at position-6 (2i-2l) have the highest cytotoxicity among those with indole functionalized at position-4 (2a-2d) or position-5 (2e-2h). From these facts, the authors concluded that hybrids with indole substituted at position-4 can represent potential candidates as antiproliferative applicants. Moreover, hybrid 2i may serve as a valuable model for creating potent anti-breast cancer therapies. Key words: Indole, Coumarin, Cytotoxicity, MTT, Michael addition, Anti-breast cancer