Synthesis of novel 6-aminocoumarin derivatives as potential –biocompatible antimicrobial and anticancer agents.

• In the literature, no 6-aminocoumarin (6-amino-COM) with a free amino group that has been biomedically investigated. • Nine novel 6-amino-COMs were synthesized in a one-pot reaction from acetaminophen with confirmed structures. • The anticancer and antimicrobial activities were studied against six cancer-derived cells and ten pathogenic microbes. • The biocompatibility was also evaluated for three normal cell types and three natural body bacteriomers. • The results revealed that our 6-amino-COMs have potent and wide-ranged anticancer and antimicrobial activities. • The multiple biomedical activities were coupled with high biocompatibility, projecting our compounds as valuable scaffolds. Among the most health-influencing threats, microbial infections and cancer have attracted a mounting interest in the medical field. To face these threats, research is directed to improve the currently-in-use medications and explore now bioactive agents. Given the latter approach, this work involves the synthesis of nine 6-aminocoumarins, coded ACM1 - ACM9 , starting from acetaminophen. The structural frameworks of the synthesized compounds were established by studying their charts abstracted from FTIR, 1HNMR , 13CNMR , and HRMS. The performed biomedical study was branched into two parts; the first included testing the antimicrobial characteristics of the synthesized compounds against ten pathogenic microbes using a broth-diluting method. These pathogens included four aerobic as well as four anaerobic bacterial strains, and two fungiomers. On the other hand, the MTT-probing method was employed to evaluate the anticancer properties of the synthesized compounds against six cancer-derived cellular types. The second biomedical study part involved the use of the same practical methods to explore the synthesized compounds' biocompatibility towards normal three cell types and three bacterial strains. Compared to the references used, the results of the first study revealed that the synthesized coumarins demonstrated potent and broad-ranged antimicrobial properties. Also, the best activity against pathogenic aerobes and fungiomers was attributed to ACM9 , with MIC values of 2 µg/ml and 1.15–1.30 µg/ml, respectively. The ACM3 exhibited the best anti-anaerobic bacterial activity, with MIC values ranging from 6 to 9 µg/ml. Given the anticancer activity, our coumarins showed encouraging outcomes, with ACM6 being the best, affording IC 50 values between 22.34 and 50.29 µg/ml. Regarding the second study, the synthesized coumarins demonstrated high biocompatibility levels toward normal cells (IC 50 values ranged from 224.59 to 248.19 µg/ml) and bacterial strains (MIC values ranged from 308 to 330 µg/ml) under investigation. From these interesting findings, the author concluded that the synthesized coumarins provided a privileged scaffold with multiple biomedical activities that varies based on the type of the substitution on the aromatic ring. [Display omitted] [ABSTRACT FROM AUTHOR]