Synthesis and Antitumor Activity of New Multifunctional Coumarins

Abstract

Cancer constitutes one of the most severe public health menaces worldwide. It is imperative to synthesize new compounds and explore their antitumor activity to find a potential resolution to this health problem. Synthesis of new scaffolds and evaluating their antitumor activity is a relevant approach for combating cancer development. Coumarins can exhibit diverse biological activities, and one of these is the antitumor activity. This study aimed to synthesize new coumarins by grafting their precursors to the aromatic amines via Schiff base formation and evaluating their introductory antitumor activity. New multifunctional coumarins (MC1-MC9) were prepared by integrating a functionalized coumarin with different toluidine derivatives via a Schiff-base linkage. Spectral characterization inspired by FTIR, 1H- and 13C- NMR spectroscopies has established the chemical structures of the synthesized products. The antitumor activity was explored in vitro versus four dominant human cancer lines, including HeLa, SKG, MCF-7, and AMN3. The outcomes acquired from the cell viability assay inspected by applying MTT dye have revealed that the synthesized multifunctional coumarins, particularly MC3, have a hopeful activity. It can be concluded that a similar trend of activity against the test cell lines was observed for the synthesized coumarins, with the best action being versus MCF-7 and the least one versus AMN3. This study not only affords a new scaffold of a significant antitumor activity but also provides some insights into its structureactivity relationship.

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“…this activity is approximately similar to those of the antioxidant and anti-inflammatory effects. Consequently, the authors might infer the anticancer activity of the semi-synthesized coumarins to their ability to quench harmful free radicals and suppress the inflammatory process [45,63]. Finally, the cytotoxicity of the semisynthesized coumarins on the utilized normal cell line is inversely related to their anticancer, antioxidant, and anti-inflammatory activities and significantly lower than that of 5-fluorouracil.…”

“…The proliferation-retardation (PR50) activity was defined as the concentration of a reference or synthesized phenolic acid-derived coumarin, at which 50% of the viable cells were proliferating retarded. This variable was calculated using nonlinear statistics from the graphical relationship between the values of PR% and their corresponding logarithmic concentrations [45].…”

“…Furthermore, FA treatment of diabetic rats was observed to restore normal blood glucose and insulin levels [19]. Coumarins are one of the most prominent families of oxygen-based heterocycles, and they have been widely used for medical and industrial applications [21]. Coumarin the class's prototype, was initially isolated from Tonka bean (coumaru) by Vogel in 1820, giving rise to the word "coumarin" [22].…”

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“…Nafacillin, naftifine, tolnaftate, and terbinafine are examples of these medications, as illustrated in Figure 2. The first albocarbon is considered an antibacterial medication, while the second and third are antifungal drugs [3].…”

“…Antitumor Activity With 18.1 million diagnoses and 9.6 million deaths recorded in 2018, cancer is the second biggest cause of morbidity and mortality worldwide [35,36]. Lung, breast, and colorectal cancers are the top three cancer phenotypes in mortality incidence [37,38]. Many attempts have been made to rehabilitate humanity's to combat this form of fatal sickness [39-47].…”