Ten coordination compounds, [Cu(L¹)Cl] (C1), [Cu(L¹)NO₃] (C2), [Cu(L²)Cl] (C3), [Cu(L²)NO₃] (C4), [Cu(L³)Cl] (C5), [Cu(L³)NO₃] (C6), [Cu(L⁴)NO₃] (C7), [Cu(L⁴)Cl] (C8), [Cu(L⁵)Cl] (C9), and [Cu(L⁵)NO₃] (C10), containing pyridine derivatives of N⁴-methoxyphenyl-thiosemicarbazones were synthesized and characterized. The molecular structure of four compounds was investigated using single crystal X-ray diffraction. Spectral analysis techniques such as FT-IR, ¹H NMR, ¹³C NMR, elemental analysis, and molar conductivity were used for all the synthesized compounds. The tested synthesized compounds were evaluated for their anticancer activity and selectivity against a variety of cancer cell lines, including HL-60, LNCaP, MCF-7, HepG-2, K-562, HeLa, BxPC-3, RD, and MDCK normal cell line. Most compounds demonstrated selective anticancer activity superior to doxorubicin. Notably, all ligands showed high antiproliferative activity against HL-60 cells, with IC₅₀ values between 0.01 and 0.06 µM and a selectivity index as high as 5000. Coordination of copper(II) with ligands HL¹ and HL³ notably enhanced antiproliferative activity, lowering the IC₅₀ to 0.03 µM. Additionally, the antioxidant activity of these compounds was assessed, revealing that all tested ligands and most coordination compounds exhibited greater antioxidant activity compared to Trolox, with some ligands showing activity up to 12.3 times higher. Toxicity studies on Daphnia magna indicated low toxicity for the ligands, generally less than doxorubicin, with LC₅₀ values ranging from 13 to 90 µM, suggesting moderate toxicity. Conversely, the coordination complexes were more toxic, with LC₅₀ values between 0.5 and 13 µM.

For the first time, a thiosemicarbazone-type ligand containing a paracetamol structural unit was synthesized. Five new coordination compounds based on copper(II) salts: [Cu(L)CH₃COO] (1), [{Cu(L)Cl}₂]·H₂O (2), [Cu(L)H₂O·DMF]NO₃ (3), [Cu(L)Br] (4), [Cu(L)H₂O]ClO₄ (5), were obtained, where HL is N-[4-({2-[1-(pyridin-2-yl)ethylidene]hydrazinecarbothioyl}amino)phenyl]acetamide. The new HL was characterized by NMR, FTIR, spectroscopy, and X-ray crystallography. All copper(II) coordination compounds were characterized by elemental analysis, FTIR, EPR spectroscopy, and molar electrical conductivity. Furthermore, single crystal X-ray diffraction analysis elucidated the structures of thiosemicarbazone HL as well as complexes 1–3. All compounds were tested for antimicrobial, antifungal, and antioxidant activities, and their toxicity to Daphnia magna was studied. Biological evaluation has revealed that most of the synthesized compounds demonstrate promising antibacterial, antifungal, and antioxidant activities. In many cases, their antibacterial/antifungal activity is comparable to that of certain drugs used in medicine for these purposes, and in some cases, even surpasses them. HL and complexes 2–5 exhibit antioxidant activity that surpasses that of Trolox. Furthermore, HL and complex 2 display virtually no toxicity to D. magna.

Fractures are becoming a bigger and bigger global health problem, with an estimated 178 million new cases each year and 455 million people living with disabilities caused by fractures. Donor site morbidity, the risk of immune rejection, and limited functional integration all make current grafting techniques less effective. Biomaterials that come from nature, like collagen, gelatin, chitosan, alginate, hyaluronic acid (HA), and silk fibroin, have become promising scaffolds because they are bioactive, mimic the extracellular matrix (ECM), and can be broken down by enzymes. Crosslinking and composite reinforcement can greatly change how well they work. For example, collagen scaffolds that are highly crosslinked with glutaraldehyde keep up to 51.9% of their tensile strength after being exposed to enzymes, while non-crosslinked scaffolds only keep 12% of their strength. Chitosan–hydroxyapatite matrices, on the other hand, can reach compressive strengths of 2–12 MPa, which is close to the strength of cancellous bone. Additive manufacturing and 4D printing allow for precise control of structures and the ability to change their shape over time, which helps with vascularization and mechanical adaptation. Injectable and in situ-forming hydrogels show clinically important results, such as filling 85% of osteochondral defects in rabbits, improving left ventricular ejection fraction by up to 9% in large-animal cardiac models, and speeding up healing by 25–40% in chronic wounds. Even with these improvements, it is still hard to get batch consistency, a standardized way to test mechanical properties, and production that meets GMP (Good Manufacturing Practices) standards and can be scaled up.

The development of antibiotic resistance, new pandemics and the rise of cancer cases are among the main challenges for modern society. Solving these problems is directly linked to the synthesis of new substances with the necessary biological effects. A big perspective presents the class of substances called thiosemicarbazones. Their representatives are already used in the pharmaceutical industry, for example Ambazone or Triapine. In general, thiosemicarbazones exhibit a wide range of useful biological activities, including antibacterial, antifungal and anticancer. It is known that coordination of thiosemicarbazones in many cases leads to enhanced biological activity. In this work, 5 copper (II) coordinative compounds based on a thiosemicarbazone have been synthesized. Antimicrobial and antifungal properties of the synthesized substances were evaluated.

Introduction. The increasing number of cancer diagnoses is a pressing issue in modern medicine. One contributing factor to cancer development is oxidative stress caused by free radicals, which can damage proteins, lipids, and DNA. Antioxidants are commonly used to mitigate these effects by neutralizing free radicals and reducing their harmful impact. Recent studies have shown that thiosemicarbazones may have antioxidant properties. These compounds are also known for their potential as anticancer, antibiotic, and antifungal agents. In this research, a series of thiosemicarbazones were synthesized and their antioxidant capacity was evaluated. Additionally, the ADME (Absorption, Distribution, Metabolism, Excretion) parameters of the synthesized compounds were evaluated to determine their potential as pharmaceutical candidates. Material and methods. All starting reagents were purchased from Sigma Aldrich or Alfa Aesar. The synthesis of the compounds was carried out using classical methods, adopted for this study. ADME analysis was performed using ADMETLabs 3.0 platform. Antioxidative properties were investigated using the standard assay method. Results. Five thiosemicarbazones were synthesized. The presence of characteristic functional groups was confirmed by FTIR spectroscopy. Synthesized compounds have a good ADME profile, characteristic of biologically active compounds. It was found that compounds 1 and 5 exhibit antioxidative activity in 6 times and 3 times higher than Trolox.

În acest articol sunt descrise metode de sinteză și analiza fizico-chimică a 5 compuși coordinativi în baza ionului de Cu(II) și 4-ciclohexil-tiosemicarbazona aldehidei 3-etoxisalicilice. În primul pas a fost efectuată sinteza ligandului prin intermediul a două metode clasice cu perfecționarea ulterioară, obținându-se astfel H2L în calitate de chelator al ionilor de cupru(II). Pentru cercetarea structuri și geometria 4-ciclohexil- tiosemicarbazonei aldehidei 3-etoxisalicilice a fost aplicată spectroscopia 1H, 13C și 15N-RMN, 13C- DEPT- 135 RMN și 15N HSQC-RMN. Substanțele sintetizate au fost analizate prin intermediul metodelor moderne de cercetare precum: spectroscopia FTIR, UV-vis și analizei elementale, difracția razelor X pe monocristal; activitatea biologică este în proces de studiu. Cuvinte-cheie: compuși coordinativi, 4-ciclohexil-tiosemicarbazone, aldehida 3-etoxisalicilică. DOI: https://doi.org/10.59295/sum1(171)2023_26