Search Results (17)

Coordination complexes play a crucial role in modern research. 4-benzopyranone-2-carboxylic acid is a fascinating class of molecules with numerous applications, including the synthesis of pharmaceuticals and valuable chiral compounds. Antibacterial and tuberculostatic medicines, HIV protease inhibitors, intermediates in organic synthesis, and organic catalysis are only a few of the biological applications of chiral complexes. In this study, the synthesis of four metal complexes, C₃₀H₂₈N₂NiO₁₂ [Ni(bzpyr)₂(py)₂(H₂O)₂] (I), C₃₀H₂₄CoN₂O₁₀ [Co(bzpyr)₂(py)₂(H₂O)₂] (II), C₂₀H₂₀O₁₃Zn [Zn(bzpyr)₂(H₂O)₃] (III), and C₃₀H₂₂CuN₂O₉ [Cu(bzpyr)₂(py)₂(H₂O)] (IV), is reported via direct reactions of 4-benzopyranone-2-carboxylic acid with metal salts and pyridine in anhydrous ethanol. Single-crystal X-ray diffraction analysis revealed that complexes I and II crystallize in the chiral space group P-1, whereas III and IV crystallize in the centrosymmetric space group P2₁/c. The structures of these complexes were further characterized by infrared spectroscopy, UV-Visible Diffuse Reflectance Spectroscopy, electrospray ionization mass spectrometry (ESI-MS), elemental analysis, nuclear magnetic resonance, electron paramagnetic resonance spectroscopy and single-crystal X-ray diffraction. In addition, the cytotoxic activities of complexes I–IV were evaluated against the human tumor cell lines K562, A549, HepG2, MDA-MB-231, and SW480, and molecular docking studies were conducted on the four complexes. Full article

N-acyl hydrazone (NAH) is recognized as a promising framework in drug design due to its versatility, straightforward synthesis, and attractive range of biological activities, including antimicrobial, antitumoral, analgesic, and anti-inflammatory properties. In the global context of increasing resistance of pathogenic bacteria to antibiotics, NAHs represent potential solutions for developing improved treatment alternatives. Therefore, this research introduces six novel derivatives of (EZ)-N’-benzylidene-2-(6-chloro-9H-carbazol-2-yl)propanehydrazide, synthesized using a microwave-assisted method. In more detail, we joined two pharmacophore fragments in a single molecule, represented by an NSAID-type carprofen structure and a hydrazone-type structure, obtaining a new series of NSAID-N-acyl hydrazone derivatives that were further characterized spectrally using FT-IR, NMR, and HRMS investigations. Additionally, the substances were assessed for their tuberculostatic activity by examining their impact on four strains of M. tuberculosis, including two susceptible to rifampicin (RIF) and isoniazid (INH), one susceptible to RIF and resistant to INH, and one resistant to both RIF and INH. The results of our research highlight the potential of the prepared compounds in fighting against antibiotic-resistant M. tuberculosis strains. Full article

Tuberculosis is an infectious disease caused by the bacterial complex Mycobacterium tuberculosis. Despite the decline in the incidence and mortality of this disease over the years, the emergence of new strains of tuberculosis resistant to existing tuberculostatic drugs is currently one of the largest public health problems. The engineering and development of new drugs is a complex process; therefore, the modification and enhancement of the drugs already marked is a better and faster solution. Ethambutol (ETB) is an antimycobacterial drug used to treat tuberculosis; however, it is highly hygroscopic and is sparingly soluble in water. Therapeutic Deep Eutectic Solvents (THEDESs) are known to improve drug solubility, permeability, and hygroscopicity, among others. In this study, three THEDESs of ETB were synthesized with sucralose, glucose and glycerol and then encapsulated in nanostructured lipid carriers to improve their stability. This work is a proof of concept on the possibility of encapsulating the THEDESs, and results show that the encapsulation of ETB is possible, yielding formulations with a loading capacity superior to 8.5% and able to incorporate THEDESs and not just ETB. Full article

Tuberculosis Peritonitis is a serious condition, whose diagnosis is established late due to the nonspecific nature of the clinical features, which delays the performance of imaging investigations and, implicitly, the setting of the diagnosis through biopsy and histopathological examination. We report the case of a 49-year-old man who presented in our clinic with nonspecific symptoms and significant nitrogen retention, with ascites fluid detected during the clinical–paraclinical examination, ultimately confirming the diagnosis of bacillary peritonitis. Confirmation of tuberculous etiology through biopsy and/or bacteriological examination is sovereign for the diagnosis. The therapeutic protocol includes three anti-tuberculostatic drugs, for a period of at least 6 months, with or without the combination of corticosteroid therapy during the first months of treatment. The patient evolution under treatment was initially favorable, but due to peritoneal adhesions, it underwent complications later. Full article

To investigate how structural modifications affect tuberculostatic potency, we synthesized seven new piperidinothiosemicrabazone derivatives 8–14, in which three of them had a pyrazine ring replacing the pyridine ring. Derivatives 8–9 and 13–14 exhibited significant activity against the standard strain (minimum inhibitory concentration (MIC) 2–4 μg/mL) and even greater activity against the resistant M. tuberculosis strain (MIC 0.5–4 μg/mL). Additionally, the effects of compounds 8–9 were entirely selective (MIC toward other microorganisms ≥ 1000 μg/mL) and non-toxic (IC50 to HaCaT cells 5.8 to >50 μg/mL). The antimycobacterial activity of pyrazine derivatives 11–12 was negligible (MIC 256 to >500 μg/mL), indicating that replacing the aromatic ring was generally not a promising line of research in this case. The zwitterionic structure of compound 11 was determined using X-ray crystallography. Absorption, distribution, metabolism, and excretion (ADME) calculations showed that all compounds, except 11, could be considered for testing as future drugs. An analysis of the structure–activity relationship was carried out, indicating that the higher basicity of the substituent located at the heteroaromatic ring might be of particular importance for the antituberculous activity of the tested groups of compounds. Full article

Hemophagocytic lymphohistiocytosis (HLH) is a condition of immune dysregulation and hyperinflammation, leading to organ failure and death. Malignancy, autoimmune conditions, and infections, including Mycobacterium tuberculosis (TB), are all considered triggers of HLH. The aim of this study was to review all reported cases of TB-associated HLH in English literature, and to summarize the epidemiology, diagnostics, treatment, and mortality in patients with concomitant HLH and TB. A systematic review of described cases with TB-associated HLH, via a structured literature search in the medical database PubMed, is presented. Additional articles were included through cross-referencing with existing review articles. Articles were reviewed based on a predetermined set of criteria. A total of 116 patients with TB-associated HLH were identified with a male:female ratio of about 3:2. The age at presentation ranged from 12 days to 83 years. Malignancy, autoimmunity, and renal failure were the most common comorbid conditions. Most patients received both tuberculostatic and specific immunomodulating treatment, which was associated with a 66% (48/73) survival rate compared to 56% (15/27) in those receiving only tuberculostatic treatment, and 0% (0/13) in those receiving only immunomodulating treatment. The survival rate was 55% overall. The overlapping presentation between disseminated TB and HLH poses challenging diagnostics and may delay diagnosis and treatment, leading to increased mortality. TB should be considered as a potential trigger of HLH; clinicians’ knowledge and awareness of this may result in the appropriate investigations needed to ensure diagnosis and proper treatment. Full article

This study aimed to develop a prolonged-release system based on palygorskite and chitosan, which are natural ingredients widely available, affordable, and accessible. The chosen model drug was ethambutol (ETB), a tuberculostatic drug with high aqueous solubility and hygroscopicity, which is incompatible with other drugs used in tuberculosis therapy. The composites loaded with ETB were obtained using different proportions of palygorskite and chitosan through the spray drying technique. The main physicochemical properties of the microparticles were determined using XRD, FTIR, thermal analysis, and SEM. Additionally, the release profile and biocompatibility of the microparticles were evaluated. As a result, the chitosan–palygorskite composites loaded with the model drug appeared as spherical microparticles. The drug underwent amorphization within the microparticles, with an encapsulation efficiency greater than 84%. Furthermore, the microparticles exhibited prolonged release, particularly after the addition of palygorskite. They demonstrated biocompatibility in an in vitro model, and their release profile was influenced by the proportion of inputs in the formulation. Therefore, incorporating ETB into this system offers improved stability for the administered product in the initial tuberculosis pharmacotherapy dose, minimizing its contact with other tuberculostatic agents in the treatment, as well as reducing its hygroscopicity. Full article

The present work describes the development of a hybrid and pH-responsive system for rifampicin using the clay mineral ‘montmorillonite’ as a nanocarrier. The influence of operational variables on the drug incorporation process was evaluated using 2⁴ factorial designs. Under optimized conditions, the experiment allowed an incorporated drug dose equivalent to 98.60 ± 1.21 mg/g. Hybrid systems were characterized by different characterization techniques (FTIR, XRD, TGA, DSC, and SEM) to elucidate the mechanism of interaction between the compounds used. Through in vitro release studies, it was possible to verify the efficacy of the pH-dependent system obtained, with approximately 70% of the drug released after sixteen hours in simulated intestinal fluid. The adjustment of the experimental release data to the theoretical model of Higuchi and Korsmeyer–Peppas indicated that the release of rifampicin occurs in a prolonged form from montmorillonite. Elucidation of the interactions between the drug and this raw clay reinforces its viability as a novel carrier to develop an anti-TB/clay hybrid system with good physical and chemical stability. Full article

In this study, six new 2,6-disubstituted thiosemicarbazone derivatives of pyridine were synthesized (4–9), and their tuberculostatic activity was evaluated. All of them showed two- to eightfold higher activity (minimum inhibitory concentration (MIC) 0.5–4 µg/mL) against the resistant strain compared with the reference drug. Compounds 5 and 7, which contained the most basic substituents—pyrrolidine and piperidine—in their structure, strongly inhibited the growth of the standard strain (MIC 2 µg/mL). Furthermore, the same derivatives exhibited activity comparable to that of the reference drugs against some types of Gram-positive bacteria (MIC 0.49 µg/mL) and showed no cytotoxicity (IC50 > 50 µg/mL) in HaCaT cells. The zwitterionic structure of each compound was determined using X-ray crystallography. Absorption, distribution, metabolism, and excretion analyses showed that all compounds are good drug candidates. Thus, compounds 5 and 7 were identified as leading structures for further research on antituberculosis drugs with extended effects. Full article

Amidrazones are widely used in chemical synthesis, industry and agriculture. We compiled some of the most important findings on the biological activities of amidrazones described in the years 2010–2022. The data were obtained using the ScienceDirect, Reaxys and Google Scholar search engines with keywords (amidrazone, carbohydrazonamide, carboximidohydrazide, aminoguanidine) and structure strategies. Compounds with significant biological activities were included in the review. The described structures derived from amidrazones include: amidrazone derivatives; aminoguanidine derivatives; complexes obtained using amidrazones as ligands; and some cyclic compounds obtained from amidrazones and/or containing an amidrazone moiety in their structures. This review includes chapters based on compound activities, including: tuberculostatic, antibacterial, antifungal, antiparasitic, antiviral, anti-inflammatory, cytoprotective, and antitumor compounds, as well as furin and acetylocholinesterase inhibitors. Detailed information on the compounds tested in vivo, along the mechanisms of action and toxicity of the selected amidrazone derivatives, are described. We describe examples of compounds that have a chance of becoming drugs due to promising preclinical or clinical research, as well as old drugs with new therapeutic targets (repositioning) which have the potential to be used in the treatment of other diseases. The described examples prove that amidrazone derivatives are a potential source of new therapeutic substances and deserve further research. Full article

Three new 4-phenylpicolin derivatives with a thiosemicarbazone structure were synthesized and evaluated for tuberculostatic activity. The compounds were obtained by the condensation of methyl 4-phenylpicolonimidate with the corresponding cycloalkylamino-1-carbothiohydrazides. The ¹H NMR temperature spectra obtained showed proton lability at the nitrogen atom N2, and X-ray crystallography confirmed the zwitterionic structure of all products. ADME calculations indicate that the compounds can be tested as future drugs. All compounds were absorbed in the gastrointestinal tract. All compounds also showed very good tuberculostatic activity (MIC 3.1–12.5 µg/mL). Derivative 1b showed the best selectivity for M. tuberculosis compared to the other pathogenic species tested. The study has allowed the emergence of imine derivative 1b as a good structure for further optimization in the search for antitubercular drugs. Full article

Four novel methyl 4-phenylpicolinoimidate derivatives of hydrazone have been synthesized and evaluated for their antimicrobial activity, including tuberculostatic activity. The compounds obtained are condensates of hydrazonamide or hydrazide with 5-nitro-2-furaldehyde or 5-nitro-2-thiophenecarboxaldehyde. The antimicrobial activity of the tested compounds varied. Compound 3b exhibited significant activity against the tested Gram-positive bacteria (7.8–250 µg/mL). The results of structural tests revealed that the compound is the only one obtained in the form of a Z isomer. Tuberculostatic activity tests showed higher activity of derivatives 3a and 4a containing nitrofuran systems (MICs 3.1–12.5 µg/mL). This research allowed us to identify hydrazone 3b as a starting point for further optimization in the search for antimicrobial drugs. Likewise, compound 4a appears to be a good guiding structure for use in future research on new anti-tuberculosis drugs. Full article

Tuberculosis remains one of the most common diseases affecting developing countries due to difficult living conditions, the rapidly increasing resistance of M. tuberculosis strains and the small number of effective anti-tuberculosis drugs. This study concerns the relationship between molecular structure observed in a solid-state by X-ray diffraction and the ¹⁵N NMR of a group of pyridine derivatives, from which promising activity against M. tuberculosis was reported earlier. It was found that the compounds exist in two tautomeric forms: neutral and zwitterionic. The latter form forced the molecules to adopt a stable, unique, flat frame due to conjugation and the intramolecular hydrogen bond system. As the compounds exist in a zwitterionic form in the crystal state generally showing higher activity against tuberculosis, it may indicate that this geometry of molecules is the “active” form. Full article

Nitroimidazoles are characterized by a wide range of biological activity and many of them are used as therapeutics. Moreover, some bicyclic nitroimidazooxazoles show considerable potency against Mycobacterium tuberculosis. Some authors noticed that in the case of chiral derivatives of nitroimidazodihydrooxazoles, the (R) form shows a greater tuberculostatic activity than the (S) enantiomer. This work describes the procurement of new 12 enantiomeric bicyclic derivatives of nitroimidazole. Full article

Original results are presented in the field of research that addresses the extension of the reaction of residue of acyl-thiosemicarbazide fixation on the structure of 5-nitrobenzimidazole by a sulphonic group. The aim of the study is the increase of new thiosemicarbazide derivatives’ applicative potential in the field of biochemistry, with a wide range of medical applications. The newly obtained compounds were characterized by using elemental analysis and spectral analysis (FT-IR and ¹H NMR). A study regarding the optimization of the chemical reactions was made. The performed in vitro biological tests confirmed the tuberculostatic activity of three newly obtained compounds against Mycobacterium tuberculosis. Full article