Antituberculosis Drugs Research Articles

Design, Synthesis, Evaluation, and Molecular Docking Study of Novel Quinoline Hydrazone Analogues as Anti-Tubercular Agents

Tuberculosis (TB) remains a global health concern, necessitating the continuous search for novel therapeutic agents to combat drug-resistant strains and enhance treatment efficacy. The present study focuses on designing, synthesizing, and exploring quinoline analogues as potential anti-tubercular agents. Quinoline scaffolds like bedaquiline inhibit the ATP synthase enzyme involved in energy production. A diverse library of 19 quinoline derivatives was sys tematically synthesized through rational structural modifications. The quinoline analogues were evaluated for their anti-tubercular activity against Mycobacterium tuberculosis (M.tb). Furthermore, the study delves into the molecular interactions between the synthesized quinoline derivatives and M.tb ATP synthase, shedding light on the underlying mechanisms of their anti-tubercular activity. The initial in-vitro screening revealed that some of the designed molecules were active against M.tb, making them potential candidates for further development.

Synthesis and structural elucidation of novel quaternary pyridinium salt and indolizine derivatives as an anti-tubercular agent: In Silico and In Vitro screening

The in vitro anti-mycobacterial activity of a novel series of diversely substituted quaternary pyridinium salts (3a-m) and indolizines (5a-h) were assessed against H37Rv strain of Mycobacterium tuberculosis (M.tb). The series of intermediate 1-(2-oxo-2-phenylethyl)-4-(piperidin-1-yl)pyridin-1-ium bromide, which contains a heterocyclic ring molecule, has been prepared by reacting with 4-(piperidin-1-yl)pyridine and phenacyl bromide at room temperature. The final ethyl 3-benzoyl-7-(piperidin-1-yl)indolizine-1-carboxylate analogues were prepared by using pyridin-1-ium bromide with electron-deficient acetylene, undergoing 1, 3-dipolar cycloaddition at the ambient temperature using anhydrous potassium carbonate and N, N-dimethylformamide as a solvent. All the newly synthesized compounds were characterized by spectroscopic techniques such as 1H and 13C NMR, and HRMS. All the synthesized intermediates and final compounds were evaluated for their anti-tubercular activities against H37Rv (ATCC 27294) strain. All the compounds exhibited anti-tubercular activities in the range of 12.5–50 µM. In vitro screening of all derivatives concluded that among all the screened candidates 3k emerged as an active hit with MIC 12.5 µM, 3l and 3m with MIC 25 µM.

Incidence and risk factors of antituberculosis drug-induced liver injury in India: A systematic review and meta-analysis.

Antituberculosis drug-induced liver injury (ATDILI) is a significant problem of tuberculosis treatment. This systematic review and meta‑analysis aimed at evaluating the incidence and risk factors of ATDILI in adult patients with tuberculosis in India. Five electronic databases were searched comprehensively for studies on Indian adult patients with tuberculosis investigating the incidence and/or risk factors of ATDILI. The relevant data was pooled in a random or fixed-effect model to calculate the pooled incidence with a 95% confidence interval (CI), standardized mean difference (MD) or odds ratio (OR). Following the screening of 3221 records, 43 studies with 12,041 tuberculosis patients were finally included. Based on the random effect model, the pooled incidence of ATDILI was 12.6% (95% CI, 9.9-15.3%, p < 0.001, I2 = 95.1%). The pooled incidence was higher in patients with daily treatment regimen compared to the thrice weekly regimen (16.5% vs. 3.5%). The concurrent hepatitis B or C infection, alcohol consumption and underlying chronic liver disease were associated with high incidence of ATDILI. The pooled incidence of acute liver failure (ALF) among ATDILI patients was 6.78% (95% CI 3.9-9.5%). Female gender (OR 1.24), older age (MD 0.26), lean body mass index (OR 3.8), hypoalbuminemia (OR 3.09), N-acetyltransferase slow acetylator genotypes (OR 2.3) and glutathione S-transferases M null mutation (OR 1.6) were found to be associated with an increased risk of ATDILI. The pooled mortality rate of ATDILI patients was 1.72% (95% CI 0.4-3.0%) overall and 71.8% (95% CI 49.3-94.2%) in case of ALF. Overall, 12.6% patients of tuberculosis in India developed ATDILI when combination of first-line antituberculosis drugs was used. An average of 7% of ATDILI patients progressed to ALF which had a high mortality rate. Older age, female, poor nutritional status and some genetic polymorphisms were identified as significant risk factors.

Design, synthesis and antimycobacterial activity of novel benzothiazinones with improved water solubility

Nitrobenzothiazinones (BTZs) represent a novel type of antitubercular agents targeting DprE1. Two clinical candidates BTZ043 and PBTZ169, as well as many other BTZs showed potent anti-TB activity, but they are all highly lipophilic and their poor aqueous solubility is still a serious issue need to be addressed. Here, we designed and synthesized a series of new BTZ derivatives, wherein a hydrophilic COOH or NH2 group is directly attached to the oxime moiety of TZY-5-84 discovered in our lab, through various linkers. Two compounds 1a and 3 were first reported to possess excellent activity against MTB H37Rv and MDR-MTB strains (MIC: <0.029–0.095 μM), low toxicity and acceptable oral PK profiles, as well as significantly improved water solubility (1200 and > 2000 μg/mL, respectively), suggesting they may serve as promising hydrophilic BTZs for further antitubercular drug discovery.

A cheminformatics and network pharmacology approach to elucidate the mechanism of action of Mycobacterium tuberculosis γ-carbonic anhydrase inhibitors.

Mycobacterium tuberculosis (Mtb) carbonic anhydrases (CAs) are critical enzymes that regulate pH by converting CO2 to HCO3 -, essential for Mtb's survival in acidic environments. Inhibiting γ-CAs presents a potential target for novel antituberculosis drugs with unique mechanisms of action. This study aimed to explore the biological connections underlying Mtb pathogenesis and investigate the mechanistic actions of antituberculosis compounds targeting the Cas9 protein. We employed homology modeling and virtual screening to identify compounds with high binding affinities for Cas9 protein. This study used the homology modeling approach employing high-quality AlphaFold DB models for γ-CA. Furthermore, the systems biology approach was used for analyzing the integrated modelling of compounds, integrating data on genes, pathways, phenotypes, and molecular descriptors. Single-cell RNA sequencing was also conducted to profile gene expression. Three compounds, F10921405, F08060425, and F14437079, potentially binding to Cas9 protein, have been identified. F10921405 and F08060425 showed significant overlap in their effects on pathways related to the immune response, while F14437079 displayed distinct mechanistic pathways. Expression profiling revealed high levels of genes such as PDE4D, ROCK2, ITK, MAPK10, and SYK in response to F1092-1405 and F0806-0425, and MMP2 and CALCRL in response to F1443-7079. These genes, which play a role in immune modulation and lung tissue integrity, are essential to fight against Mtb. The molecular relationship and pathways linked to the mentioned compounds give the study a holistic perspective of targeting Mtb, which is essential in designing specific therapeutic approaches. Subsequent research will involve experimental validation to demonstrate the efficacy of the promising candidates in Mtb infections.

Drug resistance and genomic variations among Mycobacterium tuberculosis isolates from The Nile Delta, Egypt

Tuberculosis is a global public health concern. Earlier reports suggested the emergence of high rates of drug resistant tuberculosis in Egypt. This study included 102 isolates of Mycobacterium tuberculosis collected from two reference laboratories in Cairo and Alexandria. All clinical isolates were sub-cultured on Löwenstein–Jensen medium and analyzed using both BD BACTEC MGIT 960 SIRE Kit and standard diffusion disk assays to identify the antibiotic sensitivity profile. Extracted genomic DNA was subjected to whole genome sequencing (WGS) using Illumina platform. Isolates that belong to lineage 4 represented > 80%, while lineage 3 represented only 11% of the isolates. The percentage of drug resistance for the streptomycin, isoniazid, rifampicin and ethambutol were 31.0, 17.2, 19.5 and 20.7, respectively. Nearly 47.1% of the isolates were sensitive to the four anti-tuberculous drugs, while only one isolate was resistant to all four drugs. In addition, several new and known mutations were identified by WGS. High rates of drug resistance and new mutations were identified in our isolates. Tuberculosis control measures should focus on the spread of mono (S, I, R, E)- and double (S, E)-drug resistant strains present at higher rates throughout the whole Nile Delta, Egypt.

Protocol for the effectiveness of multimonth refill of antituberculosis drugs (MORAD) on treatment success among people with drug-susceptible tuberculosis in rural eastern Uganda: a non-inferiority randomised trial

IntroductionMultimonth dispensing of antituberculosis (TB) drugs reduces frequent visits and costs associated with longer travel distances to a TB clinic. We will evaluate the effectiveness of multimonth dispensing of anti-TB...

Anti-tuberculosis (TB) Drug Stockouts in India: Implementation Gaps, Implications for Patients and Public Health

Anti-tuberculosis (TB) Drug Stockouts in India: Implementation Gaps, Implications for Patients and Public Health

Synthesis and in silico studies of some new pyrrolylbenzamide derivatives as antitubercular and antimicrobial agents

Eighteen new pyrrolylbenzamide derivatives (6a-6r) were synthesized by reacting N-(2,5-dimethyl- 1H-pyrrol-1-yl)-4-(2-hydrazineyl-2-oxoethoxy)benzamide (4) with substituted benzoic acids (5a-5r) in the presence of 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate, diisopropyl ethylamine and dimethyl formamide. The produced compounds were subjected to molecular docking studies against the dihydrofolate reductase (DHFR) and InhA mycobacterial enzymes. The compounds were biologically screened for antimycobacterial, and antibacterial activities along with InhA and DHFR enzyme inhibition studies. The compounds were also analyzed for ADMET parameters. The compounds 6j, 6l, 6q, and 6r exhibited good antitubercular activity, and compounds 6j, 6l, 6q, and 6r were effective against the Gram-negative Escherichia coli strain. The compounds 6b, 6f, 6j, 6l, and 6q showed good InhA inhibition and compounds 6b, 6c, 6j, 6l, and 6q were effective against DHFR enzyme. Among the synthesized compounds 6j and 6l exhibited promising antitubercular, antibacterial, and effective InhA and DHFR enzyme inhibition values.. KEYWORDS :Benzamide, Dimethylpyrrole, Antimycobacterial activity, Antibacterial activity.

Anti-tuberculosis Drugs Stock-outs: Interruptions and Implications

Anti-tuberculosis Drugs Stock-outs: Interruptions and Implications

Evaluating the efficacy of whole genome sequencing in predicting susceptibility profiles for first-line antituberculosis drugs

ObjectivesThis study aimed to examine the efficacy of whole genome sequencing (WGS) in accurately predicting susceptibility profiles, potentially eliminating the need for conventional phenotypic drug susceptibility testing (pDST) for first-line antituberculosis drugs in routine tuberculosis diagnosis. MethodsOver the period of 2017 to 2020, 1114 Mycobacterium tuberculosis complex isolates were collected with drug susceptibility testing conducted using the MGIT960 system and WGS performed for predicting drug resistance profiles. In addition, we implemented a new algorithm with an updated WGS workflow, omitting pan-susceptible strains from pDST. ResultsResults showed that out of 1075 analysed isolates, WGS-based genotypic sensitivity predictions for isoniazid, rifampicin, ethambutol, and pyrazinamide were 100% (95% CI, 99.6–100%), 100% (95% CI, 99.62–100%), 99.8% (95% CI, 99.26–99.94%), and 100% (95% CI, 99.63–100%), respectively. In contrast, the WGS-based genotypic resistance prediction, was 98.85% (95% CI, 93.77–99.79%) for isoniazid, 94.74% (95% CI, 82.71–98.54%) for rifampicin, 86.96% (95% CI, 67.87–95.46%) for ethambutol, and 75.7% (95% CI, 59.9–86.63%) for pyrazinamide. Moreover, WGS enabled the implementation of a new testing algorithm that made it unnecessary to perform pDST in 954 of all 1075 samples (88.7%) and in 890 of 901 pan-susceptible samples (98.8%). DiscussionIntegrating WGS into tuberculosis management offers significant potential to replace phenotypic drug susceptibility testing, especially for problematic drugs like pyrazinamide and ethambutol, potentially improving treatment outcomes.

Correlation Between Tuberculosis Type and Comorbidities with Nutritional Recovery Rates Post-Tuberculosis Treatment in Pediatric Patients

Background: Tuberculosis remains a significant cause of mortality in children. Nutritional status is one of the major risk factors for tuberculosis severity. This study investigated the factors influencing nutritional status in tuberculosis patients. Methods: This is a retrospective, cross-sectional study conducted in the tertiary national-referral hospital in Jakarta, Indonesia. Data were obtained from electronic health records from 2012-2018. This study included patients aged 0-18 years-old who were diagnosed and treated with anti-tuberculosis drugs. Patients who did not complete the therapy for minimum 2 months were excluded. Results: A total of 207 patients were included in this study. The type of tuberculosis was associated with the nutritional status of children after 2 months of treatment (p value = 0.014; 95% CI = 0.422 - 0.914). Children with extrapulmonary TB showed better improvement in nutritional status compared to those with pulmonary TB. Comorbidities were also associated with nutritional status (p-value = 0.020; CI95% = 1.063 - 2.382). Patient without comorbidities experience better nutritional status improvement than those with comorbidities. Conclusion: The nutritional status of tuberculosis patients improved after the 2-months of treatment. The type of tuberculosis and the presence of comorbidities influence the outcomes of nutritional status during anti-tuberculosis treatment.

Determinant of Successful Tuberculosis Treatment in UPT Puskesmas Singosari Working Areas in 2020-2022

Background: Indonesia is one of the countries that contribute the most mortality of Tuberculosis (TB) in the world. The tuberculosis treatment success rate in Indonesia is 86% which is still far from the target coverage of the TB treatment success rate (90%). This study was conducted to determine the determinant factors associated with successful TB treatment in Puskesmas Singosari.Methods: A cross-sectional design study was constructed for this study and used SITB including form TB as a research instrument. The population of this study were all drug-sensitive TB patients who had completed treatment at the Puskesmas Singosari in 2020, 2021, and QI-QII in 2022. The sample of this study was 71 people from 99 total population. The dependent variable is the success of drug-sensitive TB treatment. Independent variables are sex, age, weight, regular use of anti-tuberculosis drugs, and comorbidities. The data processing and analysis are being conducted using SPSS software.Result: Chi-square analysis showed that the variable weight changes has a significant relation to successful tuberculosis treatment (p = 0.014; OR = 9.818). This study found that the mean weight gain in patients who succeeded in TB treatment was approximately 2.19 kg.Conclusion : Puskesmas Singosari's TB Team can collaborate with the nutritionist team to optimize TB treatment through monitoring the nutritional status and weight gain of drug-sensitive TB patients.

The Impact Of Clients' Knowledge On Compliance With Anti-Tuberculosis Medication At Home

Pulmonary tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis, namely acid-fast bacteria. Successful treatment of patients with tuberculosis (TB) is a problem in today's society. One of the reasons for the increase in pulmonary TB cases is the low level of education of sufferers. One of the causes of failure of tuberculosis treatment therapy is the side effects of anti-tuberculosis drugs (OAT) which can affect the adherence to medication in tuberculosis patients. The success of TB treatment is compliance in taking anti-tuberculosis medication at the prescribed dose. The aim of this research was to determine the relationship between clients' knowledge of pulmonary tuberculosis and compliance with taking anti-pulmonary tuberculosis medication at Harapan Pematang Siantar Hospital. This research was conducted at Harapan Pematangsiantar Hospital in May 2023. This type of research is descriptive quantitative correlational with a cross-sectional approach. Data collection was carried out using a questionnaire with the Gutman scale. The population of this study was all outpatient clinic patients at Harapan Pematang Siantar Hospital in October-December 2022. The sampling technique was accidental sampling, namely 58 respondents who came in May 2023. Statistical test results used the chi square test with a confidence level of 95% (α = 0.05) shows the p value = 0.001, meaning that there is a relationship between the level of knowledge of tuberculosis clients and compliance with taking anti-tuberculosis medication at Harapan Pematang Siantar Hospital in 2023

PRIVATE SECTOR INVOLVEMENT IN TUBERCULOSIS CONTROL IN A TRIBAL DISTRICT OF MAHARASHTRA, INDIA

Introduction: In India, the private sector caters about seventy percent of TB patients. The majority of private practitioners (PPs) are not updated with current National Tuberculosis Elimination Program (NTEP) guidelines resulting in wrong diagnosis and treatment leading to irrational use of the anti-tuberculosis drugs favoring the emergence and spread of drug resistance. Objectives: 1)To assess the knowledge of PPs about diagnosis and management of tuberculosis as per NTEP guidelines 2)To know the difficulties faced by PPs during the treatment of TB patients and measures to address them as per their perspective. Methodology: Study design &amp; study setting:- a cross-sectional study was undertaken in a tribal district of Maharashtra. 86 PPs interviewed with the help of a structured questionnaire and later conducted focused group discussion (FGD). The data was analyzed with percentages and proportions. Results: The majority 65(75%) of PPs had knowledge about NTEP guidelines but only 21(25%) PPs were updated with the latest changes in the program. PPs expressed concern over the non-availability of diagnostics for extra-pulmonary TB, occasional shortage of drugs, unawareness of patients about the gravity of the disease, and treatment compliance. To address it, they felt the need for awareness activities on social media continuously, round-the-clock services for investigations, incentive for successfully completing treatment to patients along with timely updating PPs about recent updates on NTEP. Conclusion: Continuous quality training regarding basic knowledge and recent updates in NTEP for PPs should be imparted NTEP implementation at the district needs to be strengthened to overcome the difficulties mentioned by PPs.

Monitoring of adverse effects of antituberculosis drugs: case study of hepatic cytolysis and skin reactions

Introduction. Tuberculosis remains a major public health issue worldwide. Progress in treatment, particularly with the emergence of anti-tuberculosis drugs, has been significant. However, identifying the drugs responsible for adverse effects is crucial to establish a practical approach in clinical situations, including the assessment and monitoring of these effects. Methods. This case study describes the monitoring and management of adverse effects of anti-tuberculosis drugs in patients at the Tuberculosis and Respiratory Diseases Control Department (SCTMR) in Sidi Bel Abbes (Algeria). Results. The observed effects include nine cases of hepatic cytolysis and two cases of skin reactions. This work revealed a predominantly high intrinsic imputability of anti-tuberculosis drugs, with a rating of I3 (C2S2) for six cases and I5 (C2S3) for five cases. The therapeutic interventions implemented and their compliance with international recommendations are discussed. Discussion. SCTMR specialists generally follow international recommendations to manage adverse effects of antituberculosis drugs. However, the high imputability of anti-tuberculosis drugs indicates that they are strongly incriminated in the occurrence of these adverse effects. Conclusion. Adverse effects of anti-tuberculosis treatment are not rare, requiring rigorous clinical, biological and pharmacovigilance monitoring. These surveillances can reduce mortality and morbidity associated with tuberculosis treatment. A government commitment is essential to revitalize the national pharmacovigilance center and improve the detection of serious adverse effects.

A Rare Case of Pyogenic and Tuberculous Co-Infection

CNS co-infections by pyogenic and tuberculosis are uncommon infectious processes, with few cases reported to date. These superadded bacterial infections during CNS tuberculosis present usually atypical clinical manifestations. Bacterial meningitis is a rare but severe complication of patients with spondylodiscitis. CNS tuberculosis has a broad spectrum of disease patterns and a high risk of complications and mortality. Although bacterial infection of the central nervous system (CNS) is a lifethreatening neurological emergency only few papers reported. Here We report a case of 48 year old diabetic male who was diagnosed with Neurotuberculosis with bacterial meningitis and cervical spondylodiscitis and treated with both Antibiotics and Anti-Tuberculous drugs and patient improved symptomatically. Keywords: Bacterial meningitis, TB Meningitis, Cervical Spondylodiscitis, Anti-Tuberculous drugs.

Optimization of Polylactide-Co-Glycolide-Rifampicin Nanoparticle Synthesis, In Vitro Study of Mucoadhesion and Drug Release.

Despite the large number of works on the synthesis of polylactide-co-glycolide (PLGA) nanoparticles (NP) loaded with antituberculosis drugs, the data on the influence of various factors on the final characteristics of the complexes are quite contradictory. In the present study, a comprehensive analysis of the effect of multiple factors, including the molecular weight of PLGA, on the size and stability of nanoparticles, as well as the loading efficiency and release of the antituberculosis drug rifampicin (RIF), was carried out. Emulsification was carried out using different surfactants (polyvinyl alcohol, Tween 80 and Pluronic F127), different aqueous-to-organic phase ratios, and different solvents (dichloromethane, dimethyl sulfoxide, ethyl acetate). In this research, the PLGA nanoemulsion formation process was accompanied by ultrasonic dispersion, at different frequencies and durations of homogenization. The use of the central composite design method made it possible to select optimal conditions for the preparation of PLGA-RIF NPs (particle size 223 ± 2 nm, loading efficiency 67 ± 1%, nanoparticles yield 47 ± 2%). The release of rifampicin from PLGA NPs was studied for the first time using the flow cell method and vertical diffusion method on Franz cells at different pH levels, simulating the gastrointestinal tract. For the purpose of the possible inhalation administration of rifampicin immobilized in PLGA NPs, their mucoadhesion to mucin was studied, and a high degree of adhesion of polymeric nanoparticles to the mucosa was shown (more than 40% within 4 h). In the example of strain H37Rv in vitro, the sensitivity of Mycobacterium tuberculosis to PLGA-RIF NPs was proven by the complete inhibition of their growth.

Self-assembled belt[12]pyridine nanotube for the adsorption and removal of anti-TB drugs from wastewater

Environmental safety is a major concern of today's world, and it has attracted the attention of the scientific research community. The environment gets contaminated due to various toxic drugs and pharmaceutical toxins coming from different sources. Therefore, removing these toxins is necessary for making the environment greener and safer. Nanomaterials are excellent candidates for adsorption and removal of harmful materials due to their unique properties. Herein we have studied self-assembled nanotube based on belt[12]pyridine (2-(12BPy)) as an adsorbent for the removal of antituberculosis drugs i.e. isoniazid (INZ) and pyrazinamide (PZA). The adsorption ability is studied by considering the adsorption energy (Eads), non-covalent interaction index analysis (NCI), quantum theory of atoms in molecules (QTAIM), energy decomposition analysis (EDA), charge transfer via natural bond orbital analysis (NBO) and electron localization function (ELF), and dipole moment. The results indicate strong adsorption of selected drugs with self-assembled nanotube without altering the electronic properties. Recovery time of the complexes is also calculated to understand the regeneration of the nanotube. Results also demonstrate that van der Waals forces are major contributor in the adsorption of drug molecules within the nanotube. Our results indicate that belt[12]pyridine (2-(12BPy)) nanotube can be used as an adsorbent for the removal of toxic drug molecules from the environment. This research will benefit the scientists working in the field of new sensors for biological components and materials.

Design, synthesis and docking studies of new molecular hybrids bearing benzimidazole and thiazolidine-2,4-dione as potential antitubercular agents

Finding novel therapeutic medications to combat tuberculosis (TB) is crucial, as evidenced by the disease's growth as a worldwide health concern in recent decades and the rise of drug-resistant forms of Mycobacterium tuberculosis (Mtb). In this article, we describe the synthesis and design of a novel class of thiazolidine-2,4-dione derivatives (5a-i) based on 1H-benzo [d]imidazoles as antitubercular drugs. Spectroscopic techniques and elemental analysis were used to characterize each of the newly synthesized molecules. The antitubercular activity of all the newly synthesized title compounds was assessed against drug-sensitive Mtb H37Rv, multidrug-resistant (MDR-TB), and extensively drug-resistant (XDR-TB) tuberculosis. Compounds 5e and 5 h had the most antitubercular activity among all the newly synthesized hybrids against drug-sensitive, MDR-TB, and XDR-TB strains, with MIC values ranging from 0.21 to 47.84 μM. When it comes to drug-sensitive, drug-resistant, and XDR Mtb strains, compound 5 h with a trifluoromethyl group is 1.71, 10.86, and 3.50 times more potent, whereas compound 5e with a nitro group is 1.12, 8.50, and 2.61 times more active. Remarkably, the compounds' in vitro cytotoxicity test demonstrated good selectivity indices, highlighting their safety on the normal lung fibroblast (WI-38) cell line experiment. To further understand the interactions between potent hybrids and the target enzyme, molecular docking investigations were conducted against the decaprenyl-phosphoryl-ribose 2′-epimerase (DprE1) enzyme. The target protein exhibited preferentially positive interactions with the potent compounds 5e, 5f, 5 h, and 5i. Relationships between structure-activity as well as drug-likeness were used to connect the freshly synthesized compounds' physical and biological properties. When considered collectively, these results suggest that compounds 5e and 5 h might be promising candidates for the development of drug-sensitive and drug-resistant TB therapies in the future.