Search Results (77)

The coordination chemistry of a hydrazinylpyrazine-derived Schiff base ligand (L1), formed in situ from salicylaldehyde and 2-hydrazinopyrazine, with Fe(III) salts has been systematically investigated under varied synthetic conditions. Six discrete Fe(III) complexes (1a–1e and 2) were isolated and structurally characterised via single-crystal X-ray diffraction, revealing diverse coordination geometries ranging from five-coordinate pseudo-trigonal bipyramidal to six-coordinate pseudo-octahedral environments. The supramolecular architectures are governed by a rich interplay of non-covalent interactions, including hydrogen bonding, halogen bonding, and π–π stacking, which significantly influence the crystallisation pathways and final solid-state structures. Continuous shape measure (CShM) analysis highlights substantial geometric distortion in the bis-tridentate complexes, attributed to the steric and electronic constraints imposed by the ligand. Powder X-ray diffraction and infrared spectroscopy confirm the presence of multiple phases in bulk samples, underscoring the kinetic competition between crystallisation and coordination. The results demonstrate that supramolecular stabilisation of monoligated species can kinetically inhibit bis-ligation, with ligand excess and solvent polarity serving as key parameters to direct complex speciation. These findings provide insight into the delicate balance between coordination geometry, ligand strain, and supramolecular assembly in Fe(III) Schiff base complexes. Full article

Schiff base ligands prepared from salicylaldehyde and 2-, 3- and 4-methoxybenzylamine were used to prepare copper(II) complexes, characterized by spectral methods, elemental analysis and X-ray crystallography in the case of complex 4a derived from 2-methoxybenzylamine. The DNA cleavage activity of the prepared complexes was exceptional, with best activities of over 95% one-strand cleavage for 4c at 3 mM and full double-strand cleavage for complex 4a at 5 mM. Absorption titration studies with ct-DNA revealed good binding constants (at 10⁵ M⁻¹) with a decrease of up to 56% light absorption. Meanwhile, the EB–DNA displacement method and viscosity studies revealed groove binding as a possible binding mode. For BSA binding studies, all three complexes showed K_BSA values in the optimal range for reversible BSA binding (10⁴ M⁻¹). The copper(II) complexes showed significant cytotoxic effects (67–96% at 1 mM) in mitochondrial activity monitoring assays. Cytotoxicity was confirmed against cancer cell lines (A549 and HepG2) and HEL cells. The complexes 4a and 4c exhibited high activity against HepG2 cancer cells (IC50 < 22 μM), comparable to cisplatin. The radical scavenging activity was determined by the INT method with the best IC50 for 4c (189 ± 11 μM). Overall, complexes 4a and 4c with a methoxy group in the ortho and para positions show high potential in most determined activities, but mainly as DNA cleavers and as cytotoxic agents with selectivity against HepG2 cells. Full article

The interaction of manganese(II) with deprotonated 3,5–dibromo–salicylaldehyde (3,5–diBr–saloH) in the absence or the presence of the N,N′-donors 2,2′–bipyridylamine (bipyam), 2,2′–bipyridine (bipy), 1,10–phenanthroline (phen), and 2,9–dimethyl–1,10–phenanthroline (neoc) as co-ligands yielded five neutral mononuclear complexes, namely Mn(3,5-diBr-salo)₂(CH₃OH)₂] (complex 1), [Mn(3,5-diBr-salo)₂(bipyam)] (complex 2), [Mn(3,5-diBr-salo)₂(bipy)] (complex 3), [Mn(3,5-diBr-salo)₂(phen)] (complex 4), and [Mn(3,5-diBr-salo)₂(neoc)] (complex 5), respectively. The resultant complexes were characterized with physicochemical and spectroscopic techniques, and single-crystal X-ray crystallography was applied to determine the crystal structure of complex 2. The evaluation of the potential biological profile of the complexes focused on the interaction with linear calf-thymus (CT) DNA, and bovine (BSA) and human (HSA) serum albumin. According to the data derived, the complexes interact intercalatively and strongly with CT DNA and associate tightly and reversibly with both albumins studied. Full article

Antibiotic resistance is a problem repeatedly reported by health authorities. Metalloantibiotics, i.e., biologically active compounds containing one or more metal ions, can be an important resource in the fight against bacteria and fungi. Here, we report the results obtained with a panel of copper(II), nickel(II) and zinc(II) complexes with thiosemicarbazone, semicarbazone and acylhydrazone ligands on Staphylococcus aureus, Escherichia coli and Candida albicans, taken as model systems of human pathogens. To increase the solubility in water, the sulfonic group was introduced on some of the ligands, isolating them as sodium salts (NaH₂L4-NaH₂L7). Complexes 1–14 were isolated, fully characterized and the X-ray structures of 11, 12 and 13 were obtained. While all the ligands have no antimicrobial activity, the copper(II) complexes 1 and 4 and the nickel(II) complex 2, obtained from thiosemicarbazone ligands, showed good activity, in particular against S. aureus; these complexes were investigated in depth, calculating their respective IC₅₀ values (4.2 μM, 3.5 μM and 61.8 μM, respectively). It should be noted that nickel(II) complex 2 does not show hemolytic activity and has a favorable SI value. While all the copper(II) complexes completely degraded the plasmid DNA in presence of H₂O₂, nickel(II) complex 2 cleaved the plasmid DNA leading to the formation of the relaxed nicked conformation, thus suggesting a different mechanism of action. Full article

The copper(II) complexes of general formula [Cu(^GL2^H,H)(Cl)] (A4–A6, G = NO₂, H and OMe, respectively), bearing NNO tridentate Schiff base ligands (^GL2^H,H)⁻ derived from the mono-condensation of 1,3-diaminopropane and G-substituted salicylaldehydes, are here reported. The elongation of the diamine with one additional carbon atom with respect to the triad derived from ethylenediamine [Cu(^GL1^H,H)(Cl)] (A1–A3, G = NO₂, H and OMe, respectively) led to different synthetic procedures, with the difficult isolation of A6 that could be obtained only in few crystals suitable for X-ray diffractions. Operating in acidic conditions to promote the coordination of chloride and expulsion of pyridine from the complex [Cu(^GL2^H,H)(py)](ClO₄) (G = NO₂) allows for obtaining A4. On the other hand, structural rearrangement occurs when G = H, yielding the dinuclear species [Cu₂(μ-saltn)(^HL2^H,H)](ClO₄)⋅0.5MeOH (D5⋅0.5MeOH) instead of the desired A5, which can be obtained by avoiding the use of HCl and operating in the excess of LiCl. Finally, A4 and A5 were investigated as cytotoxic agents against malignant (MDA-MB-231 and 22-Rv1) and healthy (HaCaT) cell lines, and the ability of the most promising A5 to be internalized and interact with cellular targets was studied. Full article

Due to their remarkable biological and pharmacological activities such as antibacterial, antifungal, anticoagulant, antioxidant, anticancer, and anti-inflammatory properties, synthesis of coumarins and their derivatives has attracted considerable attention in research and development among both organic and medicinal chemists. In this paper, we demonstrated for the first time a two-step tandem enzymatic synthesis of coumarin bioamide derivatives through sustainable continuous-flow technology. Salicylaldehyde and dimethyl malonate were firstly reacted to obtain coumarin carboxylate methyl derivatives, which were then reacted with various biogenic amines at 50 °C for about 40 min under the catalysis of lipase TL IM from Thermomyces lanuginosus to obtain coumarin bioamide derivatives in continuous-flow reactors. Reaction parameters such as reaction solvent, reaction catalyst type, reactant ratio, residence time, reaction temperature and comparative experiments with traditional batch process were studied. Ideal product yields (62.7–87.1%) were obtained. Environmentally friendly methanol was applied as the reaction medium. Substantially shorter reaction times as well as a significant increase in the product yield were obtained as compared to the batch process. This innovative approach provides a promising green, efficient and rapid synthesis strategy for pharmaceutical synthesis and further research on novel coumarin bioamide derivatives. Full article

This study reports the synthesis, characterization, and antifungal evaluation of a series of pyridoxal and salicylaldehyde derivatives, using synthetic methodologies such as radical cyclizations and click chemistry. Compounds 6a and 6b, featuring a fused dihydrobenzoxepine-pyridine scaffold, demonstrated effective fungicidal activity with MIC values of 19 µg/mL against Cryptococcus neoformans 2807. Similarly, compound 6b exhibited notable activity with a MIC of 75 µg/mL against Candida auris PUJ-HUSI 537. Both compounds outperformed fluconazole (FLC) in these strains. In silico ADMET profiling revealed favorable pharmacokinetic properties, including blood–brain barrier penetration and drug-likeness parameters consistent with Lipinski’s rule of five. Cytotoxicity assays on human fibroblasts confirmed the low toxicity of compound 6a at the tested concentrations. These results highlight the potential of the fused dihydrobenzoxepine-pyridine scaffold as a promising antifungal candidate for further investigations. Full article

Six secondary amine derivatives derived from salicylaldehyde (SA) were successfully synthesized in good to excellent yields and evaluated for their biological activities. The synthesized compounds exhibited remarkable antioxidant properties, as determined by ABTS and phenanthroline assays. Notably, compound 2 demonstrated an IC₅₀ value of 5.14 ± 0.11 µM in the ABTS assay, approximately six to nine times lower than the standards BHT and BHA. In the phenanthroline assay, all compounds showed inhibition capacities five to ten times greater than BHT and comparable to BHA, with A_0.5 values ranging from 9.42 to 31.73 µM. Among these, compound 5 displayed the lowest A_0.5 value of 9.42 ± 1.02 µM. The anti-inflammatory activity, assessed through BSA denaturation, revealed that compounds 2 and 5 were the most promising, although their activity was moderate compared to the standard diclofenac. The insecticidal potential of the compounds was evaluated against the storage insect pest Tribolium castaneum. Among the tested derivatives, compounds 1 and 6 exhibited the highest efficacy, achieving maximum mortality rates of 73.31% and 76.67%, respectively, over a seven-day treatment period. Furthermore, the molecular geometry, electronic properties, and intramolecular interactions of all compounds were investigated using DFT calculations. Thermodynamic analyses of the antioxidant mechanisms suggested that the NH bond is the most likely site for free radical attacks. These findings underscore the significant biological potential of the synthesized salicylaldehyde-derived secondary amines. Full article

Using 5-methyl salicylaldehyde (2) as a reactant to react with different amines, 2-aminobenzimidazole (1a), 2-aminobenzothiazole (1b), and 2-aminopyridine (1c), respectively, three types of Schiff base fluorescent probes 3a–3c were designed and synthesized for selective detection of Al³⁺ in aqueous media. The structure of the compounds was acquired by ¹H NMR, ¹³C NMR, and X-ray single-crystal diffraction. Furthermore, their photochromic and fluorescent behaviors have been investigated systematically by fluorescence spectra. Compounds 3a–3c can exhibit high selectivity, sensitivity, and anti-interference properties towards Al³⁺ in aqueous media. Among them, the limit of detection (LOD) of probe 3b for Al³⁺ is 2.81 × 10⁻⁷ M. Notably, the response times of probes 3a–3c for Al³⁺ are 90 s, 80 s, and 80 s, respectively, which are much faster than most previously reported probes. The coordination stoichiometry between compounds 3a–3c and Al³⁺ has been verified to be 1:1 through the Job’s plot. After coordination with Al³⁺, the C=N isomerization of compounds 3a–3c is inhibited, leading to the closure of the excited state intramolecular proton transfer (ESIPT) effect. At the same time, the fluorescence intensity is significantly increased through chelation-enhanced fluorescence mechanism (CHEF), which is confirmed by density functional theory (DFT) calculations. In addition, probes 3a–3c can be potentially applied in the selective and high-precision detection of Al³⁺ in environmental systems. Full article

Dimethoxy derivatives of salicylaldehyde benzoylhydrazone containing a methoxy group on both aromatic rings were designed and synthesized. The compounds were obtained in high yields, and their structures were confirmed by elemental analysis and various spectral techniques. In vitro evaluation of dimethoxy hydrazones demonstrated potent activity against the leukemic cell lines at low micro- and nanomolar concentrations. Remarkably, two dimethoxy analogs showed exceptional antileukemic selectivity, with no toxicity observed in normal human embryonic kidney HEK-293 cells. In silico modeling identified likely interactions with the target, human cAbl kinase, and suggested a possible mechanism for their antileukemic activity. Full article

Crops such as tree nuts, corn and peanut are highly susceptible to infestation by the aspergilli Aspergillus flavus or Aspergillus parasiticus and subsequent aflatoxin (AF) contamination, a serious threat to public food safety. Conventional control of the aspergilli has been through the application of fungicides; however, certain fungicides at sub-optimal doses have been correlated with increased production of mycotoxins including AF. Natural products (NP) have been a potential source of antifungal agents. In this study, we performed risk assessment testing, for which thirteen NP/derivatives (generally recognized as safe) were examined at sub-inhibitory concentrations to determine the enhancement of AF production in aspergilli. We found that benzaldehyde derivatives or thymol (THY) enhanced AF production in aspergilli, while 4-isopropyl-3-methylphenol (4I3M), a synthetic analog of the NP THY and carvacrol, or salicylaldehyde (SLD) exerted a potent antifungal or mycotoxin-inhibitory effect. In seed testing (corn, pistachio kernels), SLD effectively prevented fungal growth as a fumigant, while 4I3M completely inhibited AF production at ≥1.0 mM. Therefore, we concluded that NP/derivatives that do not have any significant environmental impact can be a potent source of antifungal or anti-mycotoxigenic agents, either in their nascent form or as leads for more effective derivatives; however, NP should be applied at optimum concentrations to prevent the abnormal enhancement of mycotoxin production by fungi. Full article

Anthranilic acids, salicylaldehydes and arylboronic acids reacted in EtOH/H₂O (1/3) at 150 °C under microwave irradiation for 1 h to give, in excellent yields and purity, twenty-three bridgehead bicyclo[4.4.0]boron heterocycles via one-pot, three-component green synthesis. The scope and the limitations of the reactions are discussed in terms of the substitution of ten different anthranilic acids, three salicylaldehydes and three arylboronic acids. The replacement of salicylaldehyde with o-hydroxyacetophenone demanded a lipophilic solvent for the reaction to occur. Eight novel derivatives were isolated following crystallization in a toluene-containing mixture that included molecular sieves. The above one-pot, three-component reactions were completed under microwave irradiation at 180 °C within 1.5 h, thus avoiding the conventional prolonged heating reaction times and the use of a Dean–Stark apparatus. All derivatives were studied for their affinity to calf thymus DNA using proper techniques like viscosity and UV–vis spectroscopy, where DNA-binding constants were found in the range 2.83 × 10⁴–8.41 × 10⁶ M⁻¹. Ethidium bromide replacement studies using fluorescence spectroscopy indicated Stern–Volmer constants between 1.49 × 10⁴ and 5.36 × 10⁴ M⁻¹, whereas the corresponding quenching constants were calculated to be between 6.46 × 10¹¹ and 2.33 × 10¹² M⁻¹ s⁻¹. All the above initial experiments show that these compounds may have possible medical applications for DNA-related diseases. Full article

The first example of applying salicylaldehyde derivatives, as well as coumarin with the formyl group at the C8 position in its structure, as carbonyl partners in a three-component Passerini reaction, is presented. As a result of research on the conditions of the Passerini reaction, the important role of the hydroxyl group in the salicylaldehyde used in the course of the multicomponent reaction was revealed. When an aldehyde with an unprotected hydroxyl group is used, only two-component α-hydroxy amide products are obtained. In contrast, the use of acylated aldehyde results in three-component α-acyloxy amide products with high efficiency. The developed protocol gives access to structurally diversified peptidomimetics with good yield. The compounds were also evaluated as antimicrobial agents against selected strains of nosocomial pathogenic bacteria. The structure–activity relationship revealed that inhibitory activity is strongly related to the presence of the trifluoromethyl group (CF₃) or the methyl group at the C4 position in an unsaturated lactone ring of the coumarin scaffold. MIC and MBC studies were carried out on eight selected pathogenic bacteria strains (Gram-positive pathogenic Staphylococcus aureus strain (ATCC 23235), as well as on Gram-negative E. coli (K12 (ATCC 25404), R2 (ATCC 39544), R3 (ATCC 11775), and R4 (ATCC 39543)), Acinetobacter baumannii (ATCC 17978), Pseudomonas aeruginosa (ATCC 15442), and Enterobacter cloacae (ATCC 49141) have shown that the tested compounds show a strong bactericidal effect at low concentrations. Among all agents investigated, five exhibit higher antimicrobial activity than those observed for commonly used antibiotics. It should be noted that all the compounds tested showed very high activity against S. aureus, which is the main source of nosocomial infections that cause numerous fatalities. Additionally, the cytotoxicity of sixteen derivatives was measured with the use of the MTT test on BALB/c3T3 mouse fibroblast cell lines. The cytotoxicity studies revealed that the tested substances exert a similar or lower effect on cell proliferation than that observed for commonly used antibiotics within the range of therapeutic doses. A parallel MTT assay using ciprofloxacin, bleomycin, and cloxacillin showed that these antibiotics are more cytotoxic when tested in mammalian cells, and cell viability is in the range of 85.0–89.9%. Furthermore, we have shown that the studied coumarin-based peptidomimetics, depending on their structural characteristics, are nonselective and act efficiently against various Gram-positive and Gram-negative pathogens, which is of great importance for hospitalised patients. Full article

The chromenopyridine scaffold represents an important class of heterocyclic compounds exhibiting a broad spectrum of biological properties. This review describes novel and efficient procedures for the synthesis of this scaffold. Herein, several methods were detailed and grouped according to their starting material (e.g., salicylaldehydes, chromones, chromanones and coumarins) and respective biological activity, when reported. This review highlights the potential of the reported synthetic strategies for preparing chromenopyridine derivatives with promising biological activity, paving the way for further developments in drug discovery. Full article

This review summarizes the structural characteristics and physicochemical properties of chiral 4f and 3d-4f complexes based on enantiopure salen-type Schiff base ligands. The chirality originates from the enantiopure diamines and is imparted to the Schiff base ligands and complexes and finally to the crystal structures. The reported enantiopure Schiff base ligands derive from the condensation of aromatic aldehydes, such as salicylaldehyde and its various derivatives, and the enantiopure diamines, (1R,2R) or (1S,2S)-1,2-diamino-cyclohexane, (1R,2R) or (1S,2S)-1,2-diamino-1,2-diphenylethane, (R) or (S)-2,2′-diamino-1,1′-binaphthalene, and 1,2-diaminopropane. Full article