Novel N‐pyrocatechoyl and N‐pyrogalloyl hydrazone antioxidants endowed with cytotoxic and antibacterial activity

• Published in: Archiv der Pharmazie (Weinheim) Vol. 357; no. 5; pp. e2300725 - n/a
• Main Authors: Branković, Jovica, Matejić, Vesna, Simijonović, Dušica, Vukić, Milena D., Kačaniova, Miroslava, Živanović, Marko, Mirić, Ana, Košarić, Jelena, Branković, Marija, Petrović, Vladimir P.
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01-05-2024
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; antibacterial activity; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antioxidants; Antioxidants - chemical synthesis; Antioxidants - chemistry; Antioxidants - pharmacology; Biphenyl Compounds - antagonists & inhibitors; Biphenyl Compounds - chemistry; Biphenyl Compounds - pharmacology; Cancer; Cell Survival - drug effects; Cytotoxicity; DFT; Dose-Response Relationship, Drug; HCT116 Cells; Humans; Hydrazones - chemical synthesis; Hydrazones - chemistry; Hydrazones - pharmacology; Microbial Sensitivity Tests; Molecular Structure; Picrates - antagonists & inhibitors; polyphenolic hydrazones; Structure-Activity Relationship; antibacterial activity; DFT; antioxidants; polyphenolic hydrazones; cytotoxicity
• ISSN: 0365-6233; 1521-4184
• DOI: 10.1002/ardp.202300725

Over the years, pharmacological agents bearing antioxidant merits arose as beneficial in the prophylaxis and treatment of various health conditions. Hazardous effects of radical species hyperproduction disrupt normal cell functioning, thus increasing the possibility for the development of various oxidative stress‐associated disorders, such as cancer. Contributing to the efforts for efficient antioxidant drug discovery, a thorough in vitro and in silico assessment of antioxidant properties of 14 newly synthesized N‐pyrocatechoyl and N‐pyrogalloyl hydrazones (N‐PYRs) was accomplished. All compounds exhibited excellent antioxidant potency against the 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) radical. The extensive in silico analysis revealed multiple favorable features of N‐PYRs to inactivate harmful radical species, which supported the obtained in vitro results. Also, in silico experiments provided insights into the preferable antioxidant pathways. Prompted by these findings, the cytotoxicity effects and the influence on the redox status of cancer HCT‐116 cells and healthy fibroblasts MRC‐5 were evaluated. These investigations exposed four analogs exhibiting both cytotoxicity and selectivity toward cancer cells. Furthermore, the frequently uncovered antimicrobial potency of hydrazone‐type hybrids encouraged investigations on G+ and G– bacterial strains, which revealed the antibacterial potency of several N‐PYRs. These findings highlighted the N‐PYRs as excellent antioxidant agents endowed with cytotoxic and antibacterial features.
Novel N‐pyrocatechoyl and N‐pyrogalloyl phenolic hydrazones (N‐PYRs) were synthesized and assessed in antioxidant, cytotoxic, and antibacterial assays. The N‐PYRs exhibited excellent antioxidant potency against 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) radicals. In silico calculations provided insights into potential antioxidant pathways. Also, N‐PYRs expressed cytotoxicity and selectivity toward HCT‐116 cancer cells, as well as antibacterial activity against diverse G+ and G– strains.