Journal articles on the topic 'Tuberculostatic Agents'

A series of 2-hetaryl- and 2-(hetaryl)ylidene substituted 5-fluoro-8-nitro-1,3-benzothiazin-4-ones was synthesized by interaction of 2,6-difluoro-3-nitrobenzoylisothiocyanate with C-nucleophiles. Cyclocondensation of polyfluorobenzoylchlorides with aryl and hetaryl thioamides represents new approach to 1,3-benzothiazin-4-ones. Some compounds proved to be promising for further development of tuberculostatic agents.

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.

M. tuberculosis-positive cultures were obtained from 228 patients seen in our service and drug sensitivity assays were carried out from January 1992 to December 1994. A survey of the medical records of these patients showed resistance to one or more drugs in 47 (20.6%), 25 of whom (10.9%), who reported previous treatment, were considered to have acquired resistance. Among the antecedents investigated, only previous treatment and alcoholism were the factors independently associated with the occurrence of resistance. The survival of patients with resistant strains was lower than that of patients attacked by non-resistant M. tuberculosis. We conclude that in the present series M. tuberculosis resistance to tuberculostatic agents was predominantly of the acquired type.

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.

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.

Background: Tuberculosis (TB), a formidable global health crisis, relentlessly claims countless lives annually, perpetuating widespread morbidity and mortality. The dire need for groundbreaking treatments has ignited fervent research into innovative therapeutic paradigms. Materials and Methods: This pioneering study embarked on synthesizing an array of benzimidazole derivatives, rigorously evaluated for their antimicrobial prowess through the cutting-edge Microplate Alamar Blue Assay. This sophisticated method meticulously determined the Minimum Inhibitory Concentration (MIC) against the formidable Mycobacterium tuberculosis H37Rv strain, setting a new benchmark for precision in anti-tubercular research. Results: From this ambitious endeavour, 1,2,4-triaole derivatives 3 emerged as titans, showcasing unparalleled potency against M. tuberculosis. Their remarkable anti-tubercular activity signals a monumental leap forward in combating this relentless pathogen. Conclusion: This trailblazing study emphatically validates the transformative power of synthetic chemistry in sculpting novel anti-tubercular agents. The extraordinary efficacy of compounds 3 heralds their potential as revolutionary therapeutic frontrunners, poised to redefine TB treatment landscapes. These findings galvanize further exploration and clinical scrutiny, promising to alleviate the global TB burden and usher in a new era of hope for millions afflicted by this devastating disease.

IntroductionTuberculosis is still a challenging disease, infecting around a third of the world’s population. As comorbidity with mental disorder is common, it is relevant to associate them at a diagnostic, therapeutic and prognostic level.ObjectivesWe present a clinical case describing a patient with psychosis, further diagnosed with tuberculosis during psychiatric treatment. Moreover, we present a summarized revision of the state of the art.MethodsRevision of the state of the art, drawing from PubMed and using the keywords “mental health”, “psychosis” and “tuberculosis”, in the last 10 years.ResultsMale, 61 years old, heavy smoker and alcohol drinker. Admitted for allegedly feeling “worms” in his body. After medical examination, a weight loss of 13 kg in five months and symptoms compatible with tenesmus stood out. Following diagnostic tests, the patient was diagnosed with Ekbom Syndrome and Ganglionar Tuberculosis; he was then medicated with the adequate antipsychotic and tuberculostatic agents, which resulted in overall clinical improvement.ConclusionsThis case illustrates the relationship between tuberculosis and mental disorders, in a patient with a low literacy level and a precarious socioeconomic background, known risk factors for mental disorder in patients with tuberculosis and are often associated with poor therapeutic adherence. Although proper treatment of the mental disorder is key to reducing the risk of tuberculostatic dropout, the stigma of mental disorder and tuberculosis decreases the probability of these patients seeking proper treatment. Thus, we alert the medical community for the possibility of psychiatric comorbidity in patients with diagnosed tuberculosis – and vice-versa –, allowing for an early intervention,DisclosureNo significant relationships.

A 39-year-old woman was referred to the neurology department due to headache, instability and difficulty walking for 5 months. Several ancillary tests were performed. The blood test showed leucocytosis and the cerebrospinal fluid revealed an increased total protein and glucose consumption. Other infections or autoimmune causes were excluded. The MRI showed non-specific brain and spinal cord lesions. Given the findings described, a differential diagnosis between granulomatous meningoencephalitis and primary tumour or metastasis was proposed. Empirical treatment with tuberculostatic agents and corticosteroids was started. The neurological state of the patient worsened, she fell into a non-responsive coma and died in few days. The clinical autopsy performed revealed an adenoid cystic carcinoma with involvement of the central nervous system that developed leptomeningeal dissemination along the spinal cord in a fluid ‘wash’ pattern.

University Department of Chemistry, Bhavnagar University, Bhavnagar-364 002 <em>Manuscript received 6 August 1984, accepted 20 July 1985</em> Thiosemicarbazides (1) have been prepared by the reaction of initial amine, ammonia and carbon disulphide with ethanol (95%) and sodium chloroacetate, followed by addition of hydrazine hydrate. Benzaldehyde 4-(2-ethoxyphenyl)-3-thiosemicarbazones (2) have been prepared by the condensation of thiosemicarbazide (1) and different aldehydes in boiling ethanol (95%) Thiosemicarbazones (2) treated with NaOH (5%) and potassium ferricyanide solution produced thiadiazolines (3). The conden&shy;sation of thiosemicarbazones with mercaptoacetic acid gave 4-thiazolidi&shy;nones, which further reacted with different aldehydes in presence of sodium ethoxide to produce 5-arylidine derivatives.

In recent years, the epizootic and epidemic situation of tuberculosis in animals and humans has worsened sharply in Ukraine. This is facilitated by the constant change in the morphology and biological properties of the causative agent of tuberculosis, the low efficiency of existing laboratory diagnostic methods (outdated bacteriology standards that do not meet European requirements), the emergence of multi-resistant strains of mycobacteria that are difficult to treat. Therefore, in recent decades, scientists of the world have been actively working on the creation of new chemotherapeutic agents with potential tuberculocidal and tuberculostatic activity.&#x0D; In recent decades, cases of isolation of multi-resistant strains of mycobacteria have been increasingly recorded, causing infection that is difficult to treat, which poses a significant threat to the health of animals and people. The World Health Organization constantly monitors the situation of epidemic and socially significant diseases in the world. Particular attention is paid to tuberculosis. In the last decade, the WHO has developed and successfully applied the so-called DOTS strategy in the world. The essence of DOTS (Directly Observed Treatment Short-course) is strictly controlled treatment with a short course of chemotherapy. Therefore, the search for new chemotherapeutic drugs for the treatment of tuberculosis infection is a priority area of pharmaceutical chemistry.&#x0D; One of the promising similar drugs are triazole derivatives, the active development of which continues at the department of natural sciences for foreign students and toxicological chemistry of the Zaporizhzhia State Medical University. Therefore, the direction of influence of these derivatives on epizootic strains of mycobacteria, the causative agents of animal tuberculosis, is promising.

In an effort to improve the effectiveness of treatment of tuberculosis patients, clinicians have been increasingly using increased therapeutic doses of GINK drugs in recent years. Many researchers, both in experimental and clinical observations, have found the advantage of high doses of tubazide over low ones [8, 10, 11], In this regard, there has been a tendency to use tubazide 0.3 three times, i.e. 15-20 mg/kg, even in broad clinical practice. Meanwhile, such a dose in the world literature is considered high, often leading to toxic reactions. Based on the materials of Biehl and co. (1954), Costelletos and co. (1954), Benda and co. (1954), a side effect when using isoniazid at a dose of 16-24 mg / kg is observed in 28-44% of cases. At the same time, the data on the therapeutic advantage of high doses cannot yet be considered indisputable, since there is a message about the absence of an additional effect with an increase in the amount of the drug administered [7]. The purpose of this study was to study the nature and frequency of side effects of tubazide, used 0.3 3 times a day, compared with average doses and the possibility of preventing toxic-allergic reactions with pyridoxine. There were 807 patients with fresh and chronic forms of pulmonary tuberculosis under observation (age - from 18 to 68 years). 210 people received tubazid 0.15 3 times a day and 597 - 0.3 3 times a day in combination with other tuberculostatic agents of the I or II series. Some patients receiving high doses of tubazide were given pyridoxine to prevent side effects.

Organotin(IV) and palladium(II) complexes are mainly synthesized by treating a N,O or S donor ligand with an organotin halide and PdCl2, respectively. The structures of the complexes can be elucidated by various characterization techniques such as microanalysis (CHNS), FTIR spectroscopic analysis, UV-Visible spectroscopy, NMR (1H &amp; 13C) and single crystal XRD. Organotin compounds are applied in numerous biocidal formulations as wood preservatives, surface disinfectants, antitumor agents, insecticides, marine antifouling paints, mollucides, miticides and fungicides. The biochemical activity is mainly affected by coordination number of tin, number and nature of the organic group bonded to tin and the chain length of an alkyl groups. Organotin(IV) dithiocarbamates are famous for their acaricidal, antifungal, tuberculostatic, antibacterial and anticarcinogenic activities. Cisplatin which is a famous Pt(II) drug, is successfully applied either alone or in various combinations to treat cancer. However, There is also a growing interest in the discovery of alternate drugs with palladium(II) because there are considerable similarities between the coordination chemistry of palladium(II) and platinum(II) compounds. However, the palladium complexes dissociate readily and form reactive species which could not reach their pharmacological targets. This drawback can be overcome by synthesizing Pd(II) complexes with chelating ligands such as dithiocarbamates. Pd(II) and Pt(II) compounds with bioactive ligands are of special interest due to their possibility of oral administration, lower toxicity and their ability to coordinate with DNA. Organotin(IV) derivatives possess strong antibacterial and antifungal potential while palladium(II) complexes are chiefly famous for their antitumor and anticancer activities. The nature of a metal coordinated to the ligand, has a decisive role in biological activities of both kinds of compounds.

The predisposition of patients with acute leukemia (АL) to various infectious complications is a well-known fact. The reason is a decrease in immunity due to the underlying disease and due to the use of immunosuppressive cytostatic and radiotherapy. Tuberculosis infections (TIs) are serious and life-threatening complications in patients with malignant hematological disorders and recipients after hematopoietic stem cell transplantation. Verification of tuberculosis (TB) is often delayed among patients with hematooncological diseases due to low suspicion and due to the search for other infectious complications. Those with the involvement of the respiratory system are the most common complications in immunologically compromised patients. In acute leukemia, the TB process may have been underestimated, due to negative tests for mycobacterium tuberculosis (MBT), and patients with neoplasia are often prescribed antibacterial agents such as amikacin and ftorchinolones, which are also effective against TI. We describe a 10-year-old boy who was diagnosed with pulmonary tuberculosis, a disseminated form complicated by hydrothorax, during induction chemotherapy for acute promyelocytic leukemia (APL). For diagnostic purposes, repeated punctures of the pleural cavity with drainage of pathological effusion and diagnostic and remedial bronchoscopy were performed, bacterial pneumonia and systemic mycosis were suspected. The diagnosis of TB was verified on the basis of positive PCR test for TB, molecular genetic study of sputum, bronchial lavage for the presence of genome of MBT without resistance to rifampicin, sputum microscopy, while sputum culture and pleural fluid were negative for MBT. TB treatment was coEadministered with AML-BFM 2004 intensive cytostatic therapy without dose reduction of cytostatics. The child was prescribed intensive tuberculostatic therapy with 4 drugs (rifampicin + isoniazid + pyrazinamide + inbutol) for 3 months and subsequent maintenance antituberculous chemotherapy with two drugs for 4 months (rifampicin + isonimazide). With this analysis, we advocate the need for early suspicion of TB in patients receiving treatment for AL. The results of our study suggest that antitumor chemotherapy is not an obstacle to effective TB-treatment. The described patient is in remission of AML and TB for 21 months. The research was carried out in accordance with the principles of the Helsinki declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: acute promyelocytic leukemia, tuberculosis, cytostatic therapy, children.

Abstract Background/purpose Serpiginous-like choroiditis is a rare immune-mediated sub-entity of tubercular uveitis with a usually deleterious outcome. Treatment is still controversial. The purpose in this case series is to indicate that only aggressive treatment comprising multiple anti-tubercular and multiple immunosuppressive agents seems to be able to halt the disease progression. Methods This retrospective case series included patients diagnosed with Interferon Gamma Release Assays (IGRA) -positive serpiginous choroiditis, seen at the Centre for Ophthalmic Specialized Care, Lausanne, Switzerland, treated with combined multiple antitubercular and immunosuppressive agents at presentation and having a sufficient follow-up. Disease history before referral, appraisal of disease, treatment modalities and follow-up were analyzed. Inclusion criteria were positive IGRA patients with serpiginous choroiditis with complete Spectral-Domain Optic coherence tomography (SD-OCT) and angiography images. Results From 2001 to 2020, 24 of 1525 new patients (0.26%) were diagnosed as serpiginous choroiditis. 10/24 were related to tuberculosis (positive IGRA and/or hyper-positive Mantoux test), 8/24 were IGRA negative and in 6 there was no information available. 4/10 tuberculosis related serpiginous patients fulfilled the inclusion criteria. Mean age was 39 ± 5.3 years. Snellen best corrected vision acuity (BCVA) at presentation in 3/4 where the macula was preserved was 0.96 ± 0.08. In 3/4 patients, treatment with multiple tuberculostatic therapy combined with multiple immunosuppressive agents, started at presentation or in the initial months after the first consultation, was shown to stop the progression of the disease, with a retained visual acuity of 1.0. One patient with macular involvement and a bilateral visual acuity of hand movements after 11 years of insufficient treatment, improved his visual acuity to 0.25 OD and 0.05 OS and presented a substantial visual field improvement that stabilized once multiple anti-tubercular and immunosuppressive therapy was introduced. Conclusion IGRA-positive serpiginous choroiditis (serpiginous-like choroiditis) could be halted by combined multiple tuberculostatic and multiple immunosuppressive agents, as seen in our study where 3/4 early treated patients had conserved central function and one late treated patient had recovered a substantial amount of visual field. In all 4 patients this treatment regimen halted the progression of the disease.

Tuberculosis is an airborne disease caused by Mycobacterium tuberculosis and remains one of the leading causes of death worldwide. The rise in multidrug-resistant strains has prompted the search for novel strategies to produce tuberculostatic agents. This research is aimed at developing a derivative of ethambutol by gamma radiation-induced polymerization with polyethylene glycol (PEG). The synthesis was verified by Raman spectroscopy and UV–Vis spectrometry. The results show that PEG can be chemically bonded to ethambutol by amine and alcohol groups. In in vitro biological evaluation, PEGylated and neat ethambutol showed similar cell viabilities, while the modified drug lowered bacterial growth inhibitory activity. A mechanism for the polymerization is proposed. The particle size increased for PEGylated drugs concerning the starting polyether. Despite the low antimycobacterial activity in vitro, the product seems to be a promising tool for the rapid screening of hydrolase activity.

&lt;strong&gt;Background.&lt;/strong&gt; Standard antituberculosis treatment and highly active antiretroviral therapy are frequently associated with hepatotoxicity leading to drugs discontinuation.&lt;br /&gt;&lt;strong&gt;Objective.&lt;/strong&gt; This study aimed to assess the signs of hepatotoxicity in albino rats in case of simultaneous usage of tuberculostatics (TBS) and antiretroviral agents (ART).&lt;br /&gt;&lt;strong&gt;Methods.&lt;/strong&gt; Healthy rats were divided in 4 groups: 1st control group; 2nd group was given tuberculostatics (isoniazid – 50 mg/kg, rifampicin – 50 mg/kg and pyrazinamide – 1500 mg/kg); 3rd group was given ART (efavirenz – 150 mg/kg and stavudine – 5 mg/kg); 4th group was given TBS and ART. The animals were sacrificed painlessly on the 29th day; blood and liver samples were obtained. The main biochemical and histopathological indices were determined.&lt;br /&gt;&lt;strong&gt;Conclusions.&lt;/strong&gt; Comparing with control group, repeated usage of TBS caused the prominent liver injury with cytolysis and cholestasis signs, decreasing of CYP3A and CYP2E1 isozymes activity and dysfunction of protein synthesis by the liver. ART (efavirenz and stavudine) caused the elevation of transaminases activity with the increase of serum bilirubin level at the background of increase in cytochrome 450 isoforms 3A and 2E1 activities and total serum protein. The antiretroviral agents in case of simultaneous administration with the antituberculosis drugs diminished the hepatotoxic effects of first-line drugs for tuberculosis treatment which was confirmed by the study of liver histopathology. Such results of our experimental study give encouragement for further detailed clinical research of drug-drug interaction of both pharmacological groups due to the rising cases of HIV-associated tuberculosis in the whole world.&lt;br /&gt;&lt;br /&gt;&lt;strong&gt;KEY WORDS:&lt;/strong&gt; Isoniazid, rifampicin, pyrazinamide, efavirenz, stavudine, liver, cytochrome P450.&lt;!--[if gte mso 9]&gt;&lt;xml&gt; &lt;o:DocumentProperties&gt; &lt;o:Version&gt;12.00&lt;/o:Version&gt; &lt;/o:DocumentProperties&gt; &lt;/xml&gt;&lt;![endif]--&gt;&lt;!--[if gte mso 9]&gt;&lt;xml&gt; &lt;w:WordDocument&gt; &lt;w:View&gt;Normal&lt;/w:View&gt; &lt;w:Zoom&gt;0&lt;/w:Zoom&gt; &lt;w:TrackMoves/&gt; &lt;w:TrackFormatting/&gt; &lt;w:PunctuationKerning/&gt; &lt;w:ValidateAgainstSchemas/&gt; &lt;w:SaveIfXMLInvalid&gt;false&lt;/w:SaveIfXMLInvalid&gt; &lt;w:IgnoreMixedContent&gt;false&lt;/w:IgnoreMixedContent&gt; &lt;w:AlwaysShowPlaceholderText&gt;false&lt;/w:AlwaysShowPlaceholderText&gt; &lt;w:DoNotPromoteQF/&gt; 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&lt;w:LsdException Locked="false" Priority="71" SemiHidden="false" UnhideWhenUsed="false" Name="Colorful Shading Accent 4"/&gt; &lt;w:LsdException Locked="false" Priority="72" SemiHidden="false" UnhideWhenUsed="false" Name="Colorful List Accent 4"/&gt; &lt;w:LsdException Locked="false" Priority="73" SemiHidden="false" UnhideWhenUsed="false" Name="Colorful Grid Accent 4"/&gt; &lt;w:LsdException Locked="false" Priority="60" SemiHidden="false" UnhideWhenUsed="false" Name="Light Shading Accent 5"/&gt; &lt;w:LsdException Locked="false" Priority="61" SemiHidden="false" UnhideWhenUsed="false" Name="Light List Accent 5"/&gt; &lt;w:LsdException Locked="false" Priority="62" SemiHidden="false" UnhideWhenUsed="false" Name="Light Grid Accent 5"/&gt; &lt;w:LsdException Locked="false" Priority="63" SemiHidden="false" UnhideWhenUsed="false" Name="Medium Shading 1 Accent 5"/&gt; &lt;w:LsdException Locked="false" Priority="64" SemiHidden="false" UnhideWhenUsed="false" Name="Medium Shading 2 Accent 5"/&gt; 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