Phenolic acids and their derivatives found in nature are well-known for their potential biological activity. In this study, two amides derived from trans-caffeic/ferulic acid and dopamine were synthesized and characterized by Fourier-transform infrared spectroscopy (FTIR), mass spectrometry, proton and carbon-13 nuclear magnetic resonance spectroscopy. The compounds were tested for the inhibition of acetylcholinesterase (AChE) from Electrophorus electricus and for antioxidant activity by scavenging 2,2-diphenyl-1-pycrylhydrazyl free radical (DPPH^•) and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulphonic acid) radical cation (ABTS^•+), reducing ferric ions, and ferrous ions chelation. N-trans-Feruloyldopamine displayed the highest inhibitory effect on AChE with half-maximal inhibitory concentration (IC₅₀) values of 8.52 μM. In addition, an in silico study was done to determine the most favorable AChE cluster with the synthesized compounds. Further, these clusters were investigated for binding positions at the lowest free binding energy. Both synthesized hydroxycinnamates were found to be better antioxidants than the parent acids in in vitro tests applied. N-trans-Caffeoyldopamine showed the best antioxidant activity in the three tested methods—against non-biological stable free radicals IC₅₀ 5.95 μM for DPPH^•, 0.24 μM for the ABTS^•+ method, and for reducing power (ascorbic acid equivalent (AAE) 822.45 μmol/mmol)—while for chelation activity against Fe²⁺ ions N-trans-feruloyldopamine had slightly better antioxidant activity (IC₅₀ 3.17 mM).

Background: Chlorogenic acid, an ester of caffeic acid with quinic acid, also known as 5- O-caffeoylquinic acid (5-CQA), is a ubiquitous plant constituent that is an important intermediate in lignin biosynthesis. In some cases, it occurs at surprisingly high levels in the leaves and fruits of certain higher plants, such as coffee beans. Due to its catechol moiety and an extended side chain conjugation, it easily forms a resonance-stabilised phenoxy radical, accounting for its powerful antioxidant potential. Objective: The objective of this work was to determine if the esterification and methylation of 5- CQA would enhance its antioxidant activity. Methods: Two 5-CQA derivatives were prepared for this study. Chlorogenic acid was esterified with methanol over Amberlite IR120-H to obtain methyl chlorogenate, while methyl 3',4´-dimethyl chlorogenate was prepared from 5-CQA by treatment with diazomethane. Spectroscopic methods confirmed the structure of these derivatives. Their antioxidant properties were tested to establish a relationship between structure and antioxidant activity. Results: Antioxidant activity results were generated for 5-CQA and its ester analogues using eight different methods. Depending on the method applied, results were expressed as IC50/MCE50 values or as equivalents of the applied standard (ascorbic acid and Trolox). Conclusion: In most of these tests, 5-CQA showed the highest antioxidant activity compared to its derivatives. Nevertheless, due to their hydrophobic characteristics, their ester analogues remain promising antioxidant candidates in emulsifying systems.

Phenolic aldehydes and their derivatives found in nature are well-known for their potential biological activity. In this study, four 1-substituted 1,2,3,4-tetrahydroisoquinolines (THIQs) derived from phenolic aldehydes were synthesized by phosphate buffer mediated Pictet-Spengler reaction. All derivatives were chemically and structurally characterized by elemental CHN analysis and spectroscopic methods (IR, HR-ESI-MS, 1H- and 13C-NMR). 1-Substituted THIQs derived from 3,4-dihydroxybenzaldehyde and 4-hydroxy-3-methoxybenzaldehyde were described for the first time. In order to cover the diversity of the mechanistic approach, but also to establish the relationship between structure and activity, antioxidant activity was examined by five different in vitro methods, namely: neutralization and reduction of stable free radicals 2,2-diphenyl-1-picrylhydrazyl and radical cation derived from [(2,2´-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)], ferric reducing antioxidant power, oxygen radical absorbance capacity, and ability to chelate Fe(II) ions. In vitro inhibition of acetylcholinesterase (AChE) was examined by the Ellman's colorimetric method, while computer-simulated docking was used to reveal the preferred binding site and major interaction between AChE and THIQs. Antibacterial testing was examined using the agar well method and results were presented in the form of zones of inhibition (mm).

Thalassemia, a genetic condition characterized by defective hemoglobin synthesis, is often managed with transfusion therapy, which can lead to iron overload—a significant contributor to morbidity and mortality due to organ damage and pathogenic infections. Iron chelation therapy, the cornerstone of managing iron toxicity, may inadvertently influence the gut microbiome, a critical modulator of immunity and metabolism. This review provides new insights into the interplay between iron chelation therapy and gut microbiome dynamics in thalassemia patients. It synthesizes findings on how chelators such as deferoxamine, deferasirox, and deferiprone influence microbial composition, iron availability, and systemic inflammation. Emerging evidence highlights alterations in gut microbial diversity, with reduced beneficial taxa and increased pathogenic populations, driven by changes in luminal iron levels. This imbalance contributes to immune dysregulation, systemic inflammation, and susceptibility to infections. The review advocates for tailored treatment strategies that integrate microbiome-targeted interventions alongside traditional chelation therapy to improve patient outcomes. By combining genetic profiling, dietary adjustments, and microbiome modulation, this approach offers a promising avenue for personalized medicine in thalassemia care.