Kristina Milisavljević

The search for new anticancer agents with improved efficacy and reduced toxicity has intensified interest in metal-based compounds. In this study, two novel palladium(II) complexes, synthesized from Schiff base ligands derived from 5-chloro-salicylaldehyde and p-hydroxybenzylamine or tyramine, were chemically characterized and biologically evaluated. Both complexes exhibited significant cytotoxic activity against the MCF-7 breast cancer cell line in a dose- and time-dependent manner, with Pd2 showing slightly higher potency. Morphological analysis of treated cells indicated that apoptosis is the predominant mechanism of cell death. To gain deeper insight into the potential mechanisms underlying the observed anticancer activity, several biologically relevant targets were investigated. Enzyme kinetics revealed that the complexes act as uncompetitive inhibitors of liver catalase, suggesting a possible role in the induction of oxidative stress. Fluorescence studies demonstrated that Pd2 interacts with CT-DNA through combined intercalative and minor groove binding modes and exhibits significant binding affinity toward human serum albumin, predominantly at Sudlow’s site I. Molecular docking analysis further supported favorable interactions with catalase, estrogen receptor α, and B-form DNA, providing structural insight into the experimentally observed biological effects. Overall, the study explores multiple potential mechanisms of anticancer action, underscoring the promising therapeutic potential of these palladium(II) complexes, while antitumor activity has been initially assessed using a MCF-7 cell line as a preliminary model.

A novel series of Schiff bases (3a–3k), incorporating tranexamic acid (TXA) and phenol-derived aldehydes via imine linkers, was synthesized and structurally characterized. The antimicrobial activity of the compounds was evaluated against a range of clinically and environmentally relevant bacterial and fungal strains. Among them, derivatives 3i and 3k, bearing bromine and chlorine substituents on the phenol ring, exhibited the most potent antimicrobial effects, particularly against Penicillium italicum and Proteus mirabilis (MIC as low as 0.014 mg/mL). To elucidate the underlying mechanism of action, in silico molecular docking studies were conducted, revealing strong binding affinities of 3i and 3k toward fungal sterol 14α-demethylase (CYP51B), with predicted binding energies surpassing those of the reference antifungal ketoconazole. Additionally, UV-Vis and fluorescence spectroscopy assays demonstrated good stability of compound 3k in PBS and its effective binding to human serum albumin (HSA), respectively. ADMET and ProTox-II predictions further supported the drug-likeness, low toxicity (Class 4), and favorable pharmacokinetic profile of compound 3k. Collectively, these findings highlight TXA–phenol imine derivatives as promising scaffolds for the development of next-generation antimicrobial agents, particularly targeting resistant fungal pathogens.

Tetrahydrocannabinol (THC) and its derivatives exhibit a range of pharmacological activities, making them promising candidates for neuroprotective and antioxidant applications. This study employed computational approaches, including ADMET analysis, molecular docking and quantum chemical evaluations, to investigate the pharmacokinetic properties, antioxidant potential and receptor-binding interactions of 111 THC[ ] derivatives. The ADMET analysis identified 43 derivatives with favorable pharmacokinetic profiles, reduced toxicity and synthetic accessibility. Further refinement using exclusion ([ ] and elimination ([ ] factors narrowed the selection to 16 lead candidates, among which THC6, THC32and THC53 emerged as the most promising due to their optimal balance of pharmacokinetics, synthetic feasibility and biological activity. Quantum chemical analysis of the antioxidant potential, including ionization energy (IE) and electron affinity (EA), revealed that THC6, THC32 and THC53 exhibit superior electron- donating capacities, thereby reinforcing their ability to neutralize reactive oxygen species (ROS) and mitigate oxidative stress. Molecular docking studies revealed that these three derivatives exhibited the highest binding affinity for Beta-1 Secretase (BACE1), a key enzyme implicated in neurodegenerative pathways. Notably, THC6, THC32and THC53 displayed enhanced inhibitory potential compared to THC. Furthermore, docking analysis against cannabinoid receptors CB1 and CB2 demonstrated a reduced affinity for CB1, suggesting minimized psychoactive effects, while their selective interaction with CB2 indicates potential anti-inflammatory and immunomodulatory properties. Molecular dynamics (MDs) simulations further confirmed the structural stability and favorable binding profiles of the selected derivatives in complex with BACE1, supporting their dynamic compatibility with the target enzyme. These findings highlight THC6, THC32and THC53 as leading candidates for development as antioxidant neuroprotectors. Their ability to modulate oxidative stress, inhibit neurodegenerative enzymes and selectively target cannabinoid receptors underscores their therapeutic potential. Future studies, including in vitro and in vivo evaluations, will be crucial for further validating and optimizing these promising compounds for clinical applications.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by synaptic dysfunction and neuronal loss due to the accumulation of amyloid-β peptides and tau proteins. In the pursuit of novel neuroprotective strategies, organotin(IV) compounds have garnered attention due to their unique chemical and biological properties. This study evaluates the inhibitory potential of two triphenyltin(IV) derivatives—(3-propan-1-ol)triphenyltin(IV) (Ph₃SnL₁) and (4-butan-1-ol)triphenyltin(IV) (Ph₃SnL₂)—in both free form and immobilized into mesoporous silica SBA-15~Cl, targeting acetylcholinesterase (AChE), a key enzyme involved in AD pathophysiology. The SBA-15~Cl|Ph₃SnL₂ nanostructures exhibited the most potent inhibitory activity against AChE (IC₅₀ = 0.58 μM), significantly outperforming the standard drug galantamine. Molecular docking, molecular dynamics simulations, and MM/GBSA and MM/PBSA analyses confirmed the stability and selectivity of interactions with AChE, primarily driven by hydrophobic interactions. Compound transport was also simulated using a multi-scale 3D mouse brain model to evaluate brain tissue distribution and blood–brain barrier permeability. The results highlight the strong potential of SBA-15-loaded organotin(IV) compounds as biocompatible neuroprotective agents for novel treatments of neurodegenerative diseases.

Background/Objectives: Palladium(II) complexes are promising anticancer agents with potential advantages over platinum drugs. This study aimed to synthesize and characterize three novel Pd(II) complexes (2a–c) with Schiff base ligands derived from salicylic acid and amine scaffolds, and to evaluate their antitumor activity against prostate cancer cells. Methods: The Pd(II) complexes were synthesized and structurally characterized. Cytotoxicity was tested on two human prostate cancer cell lines (PC-3, DU-145) and healthy fibroblasts (MRC-5). Apoptosis induction was assessed by flow cytometry focusing on Bcl-2 and caspase proteins. Molecular docking examined binding to androgen receptor (AR) and apoptotic regulators (CASP3, BCL2, BAX). DNA and human serum albumin (HSA) binding were also investigated. Results: All complexes showed significant cytotoxicity, with complex 2c outperforming cisplatin (IC50: 7.1 µM in DU-145; 8.6 µM in PC-3). Apoptosis was confirmed as the main cytotoxic mechanism involving Bcl-2 and caspase activation. Docking studies revealed complex 2c had the strongest binding affinity to AR and apoptotic proteins via hydrogen bonds, π–π stacking, and hydrophobic interactions. DNA and HSA binding supported their biological relevance. Conclusions: Complex 2c exhibits potent anticancer activity through apoptosis induction and dual targeting of AR and apoptotic pathways, making it a promising candidate for further anticancer drug development.