Antituberculosis Agents Research Articles

Evaluation of therapeutic effectiveness of antituberculosis injection based on conversion time in drug-resistant tuberculosis

Drug-resistant tuberculosis is a condition in which Mycobacterium tuberculosis is resistant to first-line anti-tuberculosis drugs, namely isoniazid and rifampicin, which are the two most effective anti-tuberculosis agents. Conversion time is a parameter to assess whether the therapeutic effect of injection has been achieved by carrying out two acid-resistant bacilli (ARB) sputum examinations within a maximum period of 2 consecutive months. Kanamycin and capreomycin are injectable drugs that are used in the intensive phase. This cross-sectional study aimed to evaluate the therapeutic effect of injection using ARB sputum conversion time and to analyze other factors related to ARB sputum conversion time. The study used retrospective data from patients’ medical records, collected with purposive sampling technique. The results of the study showed that from 101 patients who met the inclusion criteria 57.4% used kanamycin and 42.6% received capreomycin. The therapeutic effect was achieved in 87.1%. There was no significant correlation between the type of injection therapy and therapeutic effectiveness (p-value = 0.983). In conclusion, therapy using injections for drug-resistant tuberculosis is effective but still requires close monitoring due to the high adverse drug reaction (ADR).

Preclinical tests for salicylhydrazones derivatives to explore their potential for new antituberculosis agents

PurposeThis study target the synthesis of 22 salicylhydrazones derivatives to apply in vitro screening to explore their potential in the search for new anti-TB prototypes drugs. MethodsThe minimum inhibitory concentration (MIC) were evaluated against Mycobacterium tuberculosis (Mtb) H37Rv and clinical isolates. Drug combination assay, cytotoxicity assay, ethidium bromide accumulation assay (EtBr) and in silico analysis regarding the absorption, distribution, metabolism, excretion and toxicity (ADMET) and pharmacological properties were also performed. ResultsThree most promising compounds were selected (10, 11 and 18) to proceed with screening tests. Compound 18 presented the lowest MIC value (0.49 μg/mL) against Mtb H37Rv strain, followed by compounds 11 (3.9 μg/mL) and 10 (7.8 μg/mL). All compounds showed activity against drug susceptible and resistant clinical isolates. Cytotoxicity results were promising for all salicylhydrazones, with SI values up to 4,205 for compound 18. The derivative 10 was the only one that demonstrated a non-promising cytotoxicity scenario for a single cell line. All derivatives showed an additive effect (FICI >0.5 to 4.0) in combination with isoniazid, ethambutol and rifampicin. ConclusionAll salicylhydrazones showed potential in the screening tests performed in this study and compound 18 stood out due to its activity against susceptible and resistant bacilli at low concentrations and low cytotoxicity.

Machine Learning Approach in Dosage Individualization of Isoniazid for Tuberculosis.

Isoniazid is a first-line antituberculosis agent with high variability, which would profit from individualized dosing. Concentrations of isoniazid at 2 h (C2h), as an indicator of safety and efficacy, are important for optimizing therapy. The objective of this study was to establish machine learning (ML) models to predict the C2h, that can be used for establishing an individualized dosing regimen in clinical practice. Published population pharmacokinetic (PopPK) models for adults were searched based on PubMed and ultimately four reliable models were selected for simulating individual C2h datasets under different conditions (demographics, genotype, ethnicity, etc.). Machine learning models were trained on simulated C2h obtained from the four PopPK models. Five different algorithms were used for ML model building to predict C2h. Real-world data were used for predictive performance evaluations. Virtual trials were used to compare ML-optimized doses with PopPK model-optimized doses. Categorical boosting (CatBoost) exhibited the highest prediction ability. Target C2h can be predicted using the ML model combined with the dosing regimen and three covariates (N-acetyltransferase 2 [NAT2] genotypes, weight and race [Asians and Africans]). Real-world data validation results showed that the ML model can achieve an overall prediction accuracy of 93.4%. Using the final ML model, the mean absolute prediction error value decreased by 45.7% relative to the average of PopPK models. Using the ML-optimized dosing regimen, the probability of target attainment increased by 43.7% relative to the PopPK model-optimized dosing regimens. Machine learning models were developed with great predictive performance, which can be used to determine the individualized initial dose of isoniazid in adult patients.

Glucomannan is a promising isoniazid's enhancer that inducing macrophage phagocytosis.

Isoniazid (INH) is a frontline antituberculosis agent effective against Mycobacterium tuberculosis (Mtb), but the increasing challenge of avoiding multidrug-resistant tuberculosis, including INH resistance, necessitates innovative approaches. This study focused on enhancing macrophage phagocytosis to overcome INH resistance. Glucomannan, an immunomodulatory polysaccharide, emerged as a potential macrophage activator. Our objective was to characterize the glucomannan-INH mixture and assess its impact on INH efficacy and macrophage activity. Detailed examination of the glucomannan from Amorphophallus muelleri (0.05%-0.2%) was performed in several methods. INH sensitivity tests were carried out with the Mtb strain H37RV on Löwenstein-Jensen medium. Murine macrophage (RAW264.7) viability and activity were evaluated through MTT and latex bead phagocytosis assays. Ultraviolet-wavelength spectrophotometry was used to analyze chemical structure changes. Glucomannan (0.05%-0.2%) significantly enhanced murine macrophage viability and activity. When glucomannan was combined with INH, the IC50 value was greater compared to INH only. Phagocytosis assays revealed heightened macrophage activity in the presence of 0.05% and 0.1% glucomannan. Importantly, glucomannan did not compromise INH efficacy or alter its chemical structure. This study underscores the potential of glucomannan, particularly with a lower molecular weight, as a promising enhancer of INH, boosting macrophage phagocytosis against INH-resistant Mtb. These findings challenge the assumptions about the impact of glucomannan on drug absorption and prompt potential reevaluation. While specific receptors for glucomannan in macrophage phagocytosis require further exploration, the complement receptors are proposed to be potential mediators.

Prediction of the Potential of Benzoxazinone, 2-phenyl-4H-benzo[1,3]oxazin-4-one, and 2-[2-(4-methoxyphenyl)vinyl]-3,1-benzoxazin-4-one as New Anti-Tuberculosis

Even though it had been almost 5 decades, the decline in the prevalence of tuberculosis was still low due to the rise of drug resistance. Recently, benzoxazinone compounds began to gain potential as anti-tuberculosis agents because of their interesting structure and similarity to isoniazid, the most widely used TB drug, which had reportedly experienced many cases of resistance. This research tested the ability of the core compound benzoxazinone and its 2 derivatives to bind to the enoyl ACP-CoA receptor, which was responsible for the formation of mycobacterial walls. In silico tests were carried out using pkcsm to determine the pharmacokinetic profile, and molecular docking tests using Molegro Virtual Docker were conducted to determine the pharmacodynamic profile through binding to the enoyl ACP-CoA receptor. The selected receptors were downloaded from the protein data bank with the code 2IDZ. The research results showed that the three test compounds had good intestinal and skin absorption profiles, indicating that they could be administered orally or transdermally. The docking results, expressed by moldock score and rerank score, showed that the three test compounds had better potential compared to isoniazid. Thus, the test compounds could be developed as new anti-tuberculosis agents

Synthesis of Novel Fluoro Phenyl Triazoles Via Click Chemistry with or without Microwave Irradiation and their Evaluation as Anti-proliferative Agents in SiHa Cells.

Perform the synthesis of novel fluoro phenyl triazoles via click chemistry with or without microwave irradiation and their evaluation as anti-proliferative agents in SiHa cells. Triazoles are heterocyclic compounds containing a five-member ring with two carbon and three nitrogen atoms. They are of great importance since many of them have shown to have biological activity as antifungal, antiviral, antibacterial, anti-HIV, anti-tuberculosis, vasodilator, and anticancer agents. Synthesize novel fluoro phenyl triazoles via click chemistry and evaluate their antiproliferative activity. First, several fluorophenyl azides were prepared. Reacting these aryl azides with phenylacetylene in the presence of Cu(I) catalyst, the corresponding fluoro phenyl triazoles were obtained by two methodologies, stirring at room temperature and under microwave irradiation at 40ºC. In addition, their antiproliferative activity was evaluated in cervical cancer SiHa cells. Fluoro phenyl triazoles were obtained within minutes by means of microwave irradiation. The compound 3f, containing two fluorine atoms next to the carbon connected to the triazole ring, was the most potent among the fluoro phenyl triazoles tested in this study. Interestingly, the addition of a fluorine atom to the phenyl triazole structure in a specific site increases its antiproliferative effect as compared to parent phenyl triazole 3a without a fluorine atom. Several fluoro phenyl triazoles were obtained by reacting fluoro phenyl azides with phenylacetylene in the presence of copper sulphate, sodium ascorbate and phenanthroline. Preparation of these triazoles with MW irradiation represents a better methodology since they are obtained within minutes and higher yields of cleaner compounds are obtained. In terms of biological studies, the proximity between fluorine atom and triazole ring increases its biological activity.

Organocatalyzed Synthesis of Anti-tubercular Agents

Abstract: This review highlights synthetic developments of anti-tubercular agents by using organocatalysts. Organocatalysts-mediated synthesis is environmentally benign and highly compatible with aqueous-solvent systems, and such catalysts are attractive because of their inexpensive cost, low toxicity, good air and moisture stability and follow many principles of green chemistry. Numerous anti-tuberculosis agents have been synthesized utilizing organocatalysts and tested for their in-vivo and in-vitro anti-mycobacterial activity against Mycobacterium tuberculosis H37Rv pathogens. The inhibitory concentrations of the reported compounds were compared with the standard reference drugs in order to evaluate their inhibition potency.

Aqueous extract-mediated green synthesis of CuO nanoparticles: Potential anti-tuberculosis agents.

The emergence of drug-resistant strains in tuberculosis treatment underscores the urgency for novel therapeutic approaches. This study investigates the anti-tuberculosis activity of green-synthesized copper oxide (CuO) nanoparticles (NPs) using garlic and astragalus extracts. The physicochemical characterization of the nanoparticles confirms successful synthesis, followed by assessment of their antibacterial properties and safety profile. Rats infected with Mycobacterium tuberculosis are treated with nanocomposites derived from garlic extract at doses of 50 mg/kg and 100 mg/kg body weight. Evaluation includes the analysis of Early secreted antigenic target of 6 kDa (ESAT-6) expression and confirmation of antibodies through molecular assays. Administration of garlic and nanocomposites demonstrates significant inhibitory effects on tuberculosis progression in rats, validated by safety assessments and antibacterial efficacy. Notably, the 100 mg/kg dosage exhibits pronounced mitigation of tuberculosis-induced oxidative stress and lung damage. In conclusion, the combined administration of garlic extracts and green-synthesized nanocomposites shows promising efficacy in reducing tuberculosis infection, highlighting a potential avenue for anti-tuberculosis interventions.

Kallopterolides A-I, a New Subclass of seco-Diterpenes Isolated from the Southwestern Caribbean Sea Plume Antillogorgia kallos.

Kallopterolides A-I (1-9), a family of nine diterpenoids possessing either a cleaved pseudopterane or a severed cembrane skeleton, along with several known compounds were isolated from the Caribbean Sea plume Antillogorgia kallos. The structures and relative configurations of 1-9 were characterized by analysis of HR-MS, IR, UV, and NMR spectroscopic data in addition to computational methods and side-by-side comparisons with published NMR data of related congeners. An investigation was conducted as to the potential of the kallopterolides as plausible in vitro anti-inflammatory, antiprotozoal, and antituberculosis agents.

Dibutyltin(IV) formulations as potential antitubercular scaffold: DFT assisted emerging advances and mechanism of antitubercular action

Abstract The interplay between N,O-orthometallated, O,O′-chelated, and dibutyltin(IV) groups in biopotent hybrid formulations to combat tuberculosis is deciphered. The present study is concerned with design, generation, spectroscopic, and DFT-assisted structural characterization. It improves understanding of the structure-antitubercular activity relationship and mode of action of some dibutyltin(IV) formulations against Mycobacterium tuberculosis as possible antituberculosis agents. Dibutyltin(IV) formulations of the general formula Bu2SnLL′ (where LH = heterocyclic/non-fluorinated/fluorinated β-diketones and L′H = aminophenol/substituted aminophenols) were generated by the reaction of Bu2SnCl2 with sodium salts of the ligands in 1:1:1 molar ratio. The newly generated dibutyltin(IV) formulations were characterized with the assistance of spectroscopic techniques and mass studies. Computational calculations of some representative complexes (1 and 2) also supported the obtained spectral data. Antituberculosis activity analysis was performed on some representative dibutyltin(IV) complexes (1, 4, and 8). Out of these, complex 4 demonstrated the highest activity against Mycobacterium tuberculosis. The structure-antitubercular activity relationship and mechanism of action of the active complexes against M. tuberculosis were also investigated. An intercluster electron hopping mechanism of mode of action is suggested.

Synthesis, Biological and Molecular Docking Studies of Thiazole-Thiadiazole derivatives as potential Anti-Tuberculosis Agents.

Tuberculosis remains a global health threat, with increasing infection rates and mortality despite existing anti-TB drugs. The present work focuses on the research findings regarding the development and evaluation of thiadiazole-linked thiazole derivatives as potential anti-tuberculosis agents. We present the synthesis data and confirm the compound structures using spectroscopic techniques. The current study reports twelve thiazole-thiadiazole compounds (5 a-5 l) for their anti-tuberculosis and related bioactivities. This paper emphasizes compounds 5 g, 5 i, and 5 l, which exhibited promising MIC values, leading to further in silico and interaction analysis. Pharmacophore mapping data included in the present analysis identified tubercular ThyX as potential drug targets. The compounds were evaluated for anti-tubercular activity using standard methods, revealing significant MIC values, particularly compound 5 l, with the best MIC value of 7.1285 μg/ml. Compounds 5 g and 5 i also demonstrated moderate to good MIC values against M. tuberculosis (H37Ra). Structural inspection of the docked poses revealed interactions such as hydrogen bonds, halogen bonds, and interactions containing Pi electron cloud, shedding light on conserved interactions with residues like Arg 95, Cys 43, His 69, and Arg 87 from the tubercular ThyX enzyme.

A Comprehensive Examination of Heterocyclic Scaffold Chemistry for Antitubercular Activity.

Tuberculosis is a communicable disease which affects humans particularly the lungs and is transmitted mainly through air. Despite two decades of intensive research aimed at understanding and combating tuberculosis, persistent biological uncertainties continue to hinder progress. Nowadays, heterocyclic compounds have proven themselves in effective treatment of tuberculosis because of their wide range of biological and pharmacological activities. Antituberculosis or antimycobacterial agents encompass a broad array of compounds utilized singly or in conjunction to combat Mycobacterium infections, spanning from tuberculosis to leprosy. Here, we summarize the synthesis of various heterocyclic compounds which includes the greener synthetic route as well as use of nano compounds as catalyst along with their anti TB activities.

Photoelectrochemical sensing of isoniazid and streptomycin based on metal Bi-doped BiOI microspheres grown on book-shape layers of Ti3C2 heterostructures.

Isoniazid and streptomycin are vital drugs for treating tuberculosis, which are utilized as efficient anti-tuberculosis agents. This paper presentsa novel visible-light-driven composite photocatalyst Ti3C2/Bi/BiOI, which was built from Ti3C2 nanosheets and Bi/BiOI microspheres. Photoelectrochemical (PEC) sensors based on Ti3C2/Bi/BiOI were synthesized for isoniazid identification, which showed a linear concentration range of 0.1-125 μM with a detection limit of 0.05 μM (S/N = 3). Moreover, we designed a PEC aptasensors based on aptamer/Ti3C2/Bi/BiOI to detect streptomycin in 0.1 M PBS covering the electron donor isoniazid, because the isoniazid consumes photogenerated holes thus increasing the photocurrent effectively and preventing photogenerated electron-hole pairs from being recombined. Furthermore, PEC aptasensors based on aptamer/Ti3C2/Bi/BiOI were synthesized for streptomycin identification, which exhibited a linear concentration range of 0.01-1000 nM with a detection limit of 2.3 × 10-3 nM (S/N = 3), and are well stable in streptomycin sensing.

Fucoidan coated liposomes loaded with novel antituberculosis agent: preparation, evaluation, and cytotoxicity study

In this article, we described a novel antituberculosis imidazotetrazine derivative designed in fucoidan-coated liposomes to reduce its cytotoxicity and investigate its mucoadhesive properties. Firstly, fucoidan extracted from Ascophyllum nodosum was used for additional stabilization of liposomal suspensions and to give it mucoadhesive properties. PEG-600 and/or Tween-80 were used to increase the shelf life of liposomal suspension. The ratio of the fucoidan: lipids 1:2 was found to be the optimum that produces stable fucoidan-coated liposomes. The particle size of the optimum formulation was 336.3 ± 5.4, the PDI was 0.33, and the zeta potential was −39.6. This size and the practical spherical shape of the particles were confirmed by atomic force microscopy. In addition, the in vitro release profiles from uncoated and fucoidan-coated liposomes revealed significant and faster release compared to free antituberculosis agent. Using the MTT assay test, the fucoidan-coated liposomes exhibited fourteen times lower cytotoxicity (IC50 7.14 ± 0.91 µg/ml) than the free drug (IC50 0.49 ± 0.06). Moreover, the mucoadhesive capabilities of these liposomal formulations were also confirmed using snail mucin, which highlighting their potential use as an effective delivery system for antituberculosis therapy, with notable improvements in dissolution rate and reduced cytotoxicity.

Advances in Antiretroviral Therapy for Patients with Human Immunodeficiency Virus-Associated Tuberculosis.

Tuberculosis is one of the most common opportunistic infections and a prominent cause of death in patients with human immunodeficiency virus (HIV) infection, in spite of near-universal access to antiretroviral therapy (ART) and tuberculosis preventive therapy. For patients with active tuberculosis but not yet receiving ART, starting ART after anti-tuberculosis treatment can complicate clinical management due to drug toxicities, drug-drug interactions and immune reconstitution inflammatory syndrome (IRIS) events. The timing of ART initiation has a crucial impact on treatment outcomes, especially for patients with tuberculous meningitis. The principles of ART in patients with HIV-associated tuberculosis are specific and relatively complex in comparison to patients with other opportunistic infections or cancers. In this review, we summarize the current progress in the timing of ART initiation, ART regimens, drug-drug interactions between anti-tuberculosis and antiretroviral agents, and IRIS.

Article review: Brazilin as potential anticancer agent.

Brazilin is the main compound in Caesalpinia sappan and Haematoxylum braziletto, which is identified as a homoisoflavonoid based on its molecular structure. These plants are traditionally used as an anti-inflammatory to treat fever, hemorrhage, rheumatism, skin problems, diabetes, and cardiovascular diseases. Recently, brazilin has increased its interest in cancer studies. Several findings have shown that brazilin has cytotoxic effects on colorectal cancer, breast cancer, lung cancer, multiple myeloma, osteosarcoma, cervical cancer, bladder carcinoma, also other cancers, along with numerous facts about its possible mechanisms that will be discussed. Besides its flavonoid content, brazilin is able to chelate metal ions. A study has proved that brazilin could be used as an antituberculosis agent based on its ability to chelate iron. This possible iron-chelating of brazilin and all the studies discussed in this review will lead us to the statement that, in the future, brazilin has the potency to be a chemo-preventive and anticancer agent. The article review aimed to determine the brazilin mechanism and pathogenesis of cancer.

Rapid detection of multidrug resistance in tuberculosis using nanopore-based targeted next-generation sequencing: a multicenter, double-blind study.

Resistance to anti-tuberculous drugs is a major challenge in the treatment of tuberculosis (TB). We aimed to evaluate the clinical availability of nanopore-based targeted next-generation sequencing (NanoTNGS) for the diagnosis of drug-resistant tuberculosis (DR-TB). This study enrolled 253 patients with suspected DR-TB from six hospitals. The diagnostic efficacy of NanoTNGS for detecting Mycobacterium tuberculosis and its susceptibility or resistance to first- and second-line anti-tuberculosis drugs was assessed by comparing conventional phenotypic drug susceptibility testing (pDST) and Xpert MTB/RIF assays. NanoTNGS can be performed within 12 hours from DNA extraction to the result delivery. NanoTNGS showed a remarkable concordance rate of 99.44% (179/180) with the culture assay for identifying the Mycobacterium tuberculosis complex. The sensitivity of NanoTNGS for detecting drug resistance was 93.53% for rifampicin, 89.72% for isoniazid, 85.45% for ethambutol, 74.00% for streptomycin, and 88.89% for fluoroquinolones. Specificities ranged from 83.33% to 100% for all drugs tested. Sensitivity for rifampicin-resistant tuberculosis using NanoTNGS increased by 9.73% compared to Xpert MTB/RIF. The most common mutations were S531L (codon in E. coli) in the rpoB gene, S315T in the katG gene, and M306V in the embB gene, conferring resistance to rifampicin, isoniazid, and ethambutol, respectively. In addition, mutations in the pncA gene, potentially contributing to pyrazinamide resistance, were detected in 32 patients. Other prevalent variants, including D94G in the gyrA gene and K43R in the rpsL gene, conferred resistance to fluoroquinolones and streptomycin, respectively. Furthermore, the rv0678 R94Q mutation was detected in one sample, indicating potential resistance to bedaquiline. NanoTNGS rapidly and accurately identifies resistance or susceptibility to anti-TB drugs, outperforming traditional methods. Clinical implementation of the technique can recognize DR-TB in time and provide guidance for choosing appropriate antituberculosis agents.

Insights into the role of RAHB and IHB interactions for the structure- Activity relationship of caged xanthone Morellic Acid: Spectroscopic and DFT exploration, molecular docking, and molecular dynamics simulation studies as an Antituberculosis agent

The current study elaborates on experimental and simulated methods using density functional theory (DFT) to analyze the structure, electronic characteristics, and vibrational features of morellic acid, an isolate from Garcinia wightii. The in-depth examination of the stabilized structure indicates that the compound achieves equilibrium through conjugative, hyperconjugative, resonance-assisted hydrogen bonding (RAHB), and intramolecular hydrogen bonding (IHB) interactions, resulting in a well-supported conformation. The vibrational spectra were recorded, and the wavenumbers were comprehensively assigned using Potential Energy Distribution with a scaled quantum mechanical force field. Natural bond orbital (NBO) studies were utilized to calculate donor and acceptor bond interaction energy and electron densities. The TD-DFT computations were performed in solvent (chloroform) and gaseous phase, which agreed with the experimental values. Molecular electrostatic potential (MEP), reduced density gradient (RDG), electron localized function (ELF), and localized orbital locator (LOL) of the molecule were also analyzed. The molecular docking studies revealed that the compound holds great promise as a drug candidate for tuberculosis treatment, with the most thermodynamically stable binding score of -11.542 kcal/mol with 4BFS (protein of Mycobacterium tuberculosis PanK). The molecular dynamics (MD) simulation studies examined the stability and hydrogen bonding system of the ligand-protein complex formed between the molecule and the essential target protein for 100 ns. The findings revealed that the complex remained stable with minimal fluctuations throughout the simulation, suggesting that the molecule may prevent tuberculosis and be used as a treatment candidate.

Antitubercular evaluation of dihydropyridine-triazole conjugates: design, synthesis, in vitro screening, SAR and in silico ADME predictions.

This study investigates the potential of click chemistry for the development of novel anti-tuberculosis agents. A targeted library of 1,4-dihydropyridine-1,2,3-triazole conjugates was synthesized and evaluated for their in vitro activity against Mycobacterium tuberculosis H37Ra using the resazurin microtiter assay (REMA). Among the synthesized derivatives, compounds J10, J11, J14, J22 and J23 demonstrated significant antimycobacterial activity. These compounds exhibited low MIC values ranging from 6.24 to 6.64 μg mL-1, highlighting their promising potential as lead compounds for further developing novel tuberculosis therapeutics. In addition to the promising in vitro activity, structure-activity relationship (SAR) analysis revealed that electron-withdrawing groups on the aryl-substituted ring of the dihydropyridines (J10-J24), a triazole with an unsubstituted aryl ring or with electron-donating groups (methyl or methoxy), and a geminal dimethyl group are essential structural features for the observed antitubercular activity. Furthermore, in silico ADME (absorption, distribution, metabolism, and excretion) parameters and pharmacokinetic studies supported the potential of these conjugates for oral bioavailability. These findings collectively highlight the 1,4-dihydropyridine-1,2,3-triazole scaffold as a promising platform for developing novel orally active anti-tuberculosis drugs.

Promising Ursolic Acid as a Novel Antituberculosis Agent: Current Progress and Challenges.

Tuberculosis (TB) stands as the second most prevalent cause of global human mortality from infectious diseases. In 2022, the World Health Organization documented an estimated number of global TB cases reaching 7.5 million, which causes death for 1.13 million patients. The continuous growth of drug-resistant TB cases due to various mutations in the Mycobacterium tuberculosis (MTB) strain, raises the urgency of the exploration of novel anti-TB treatments. Ursolic acid (UA) is a natural pentacyclic triterpene found in various plants that has shown potential as a novel anti-TB agent. This review aims to provide an overview of the therapeutic prospects of UA against MTB, with a particular emphasis on in silico, in vitro, and in vivo studies. Various mechanisms of action of UA against MTB are briefly recapped from in silico studies, such as enoyl acyl carrier protein reductase inhibitors, FadA5 (Acetyl-CoA acetyltransferase) inhibitors, tuberculosinyl adenosine transferase inhibitors, and small heat shock protein 16.3 inhibitor. The potential of UA to overcome drug resistance and its synergistic effects with existing antituberculosis drugs are briefly explained from in vitro studies using a variety of methods, such as Microplate Alamar Blue Assay, Mycobacteria Growth Indicator Tube 960 and Resazurin Assays, morphological change evaluation using transmission electron microscopy, and in vivo studies using BALB/C infected with multi drug resistant clinical isolates. Besides its promising mechanism as an antituberculosis drug, its complex chemical composition, limited availability and supply, and lack of intellectual property are also reviewed as those are the most frequently occurring challenges that need to be addressed for the successful development of UA as novel anti-TB agent.