Coumarins from carcinogenic phenol: synthesis, characterization, in silico, biosafety, anticancer, antioxidant, and anti-inflammatory assessments

• Published in: Chemical papers Vol. 78; no. 1; pp. 493 - 504
• Main Author: Mustafa, Yasser Fakri
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 2024; Springer Nature B.V
• Subjects: Anticancer properties; Antioxidants; Assessments; Biochemistry; Biotechnology; Cancer; Carcinogens; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Coumarin; Free radicals; Industrial Chemistry/Chemical Engineering; Materials Science; Medicinal Chemistry; NMR; Nuclear magnetic resonance; Original Paper; Phenols; Populations; Preservatives; Carcinogenic phenol; Antioxidant; Anti-inflammatory; Biosafety; Coumarin
• ISSN: 0366-6352; 1336-9075; 2585-7290
• DOI: 10.1007/s11696-023-03105-7

Since 1947, a sterically hindered phenol named 3-( tert -butyl)-4-methoxyphenol, abbreviated here as 3-tBMP , has been widely used as a powerful preservative antioxidant for food, petrochemical, and pharmaceutical packaging. Then, the NIH considered 3-tBMP a human carcinogen based on animal experiments. This work aimed to transform this carcinogen into biosafe, biologically active coumarins using Pechmann condensation and thionyl chloride-promoted reactions. The molecular frameworks of the synthetic coumarins ( CBMPa - CBMPd ) were confirmed by various spectral detected instruments, including FTIR, 1 H-NMR, and 13 C-NMR. The in silico variables, biosafety, anticancer, antioxidant, and anti-inflammatory assessments regarding these coumarins are determined using two web-mediated free programs, two normal bacteriomers, three non-malignant cellular populations, six malignant ones, two phenotypes of free radicals, and three inflammation-mediated enzymes. The results showed that the synthetic coumarins, in particular CBMPa , showed good physicochemical and drug similarity properties in the computerized analysis. Additionally, despite the high concentrations used, the coumarins displayed biosafety profiles toward the normal bacteriomers and non-malignant cellular populations used. The constructed coumarins also displayed undetected anti-inflammatory traits along with potent antioxidant and anticancer attributes. Based on these findings, the author came to the conclusion that the carcinogenic phenol used in the experiment was converted into a biosafe antioxidant and anticancer agent with no discernible negative effects on the development of normal microbiota and healthy cellular populations. As a result, the coumarin backbone can act as a promising transformer of other phenols that cause malignancies.