Antituberculosis Activity Research Articles

TBAJ-587, a novel diarylquinoline, is active against Mycobacterium abscessus.

Nontuberculous mycobacteria (NTM) infections are extremely difficult to treat due to a natural resistance to many antimicrobials. TBAJ-587 is a novel diarylquinoline, which shows higher anti-tuberculosis activity, lower lipophilicity, and weaker inhibition of hERG channels than bedaquiline (BDQ). The susceptibilities of 11 NTM reference strains and 194 clinical Mycobacterium abscessus isolates to TBAJ-587 were determined by the broth microdilution assay. The activity of TBAJ-587 toward the growth of M. abscessus in macrophages was also evaluated. Minimum bactericidal concentration and time-kill kinetic assays were conducted to distinguish between the bactericidal and bacteriostatic activities of TBAJ-587. The synergy between TBAJ-587 and eight clinically important antibiotics was determined using a checkerboard assay. TBAJ-587 was highly effective against M. abscessus by targeting its F-ATP synthase c chain. The antimicrobial activities of TBAJ-587 and BDQ toward intracellular M. abscessus were comparable. The in vivo activities of TBAJ-587 and BDQ in an immunocompromised mouse model were also comparable. TBAJ-587 expressed bactericidal activity and was compatible with eight anti-NTM drugs commonly used in clinical practice; no antagonism was discovered. As such, TBAJ-587 represents a potential candidate for the treatment of NTM infections.

Coumarin Derivatives: Pioneering New Frontiers in Biological Applications

Abstract: Coumarins are a vital class of compounds recognized for their significant therapeutic potential, both in their natural forms and as synthetic derivatives. Characterized by a benzene ring fused to an α-pyranose ring, coumarins have garnered considerable attention from the scientific community due to their diverse pharmacological activities. This review article highlights the importance of coumarin hybrids, showcasing their enhanced biological properties and reactivity compared to traditional coumarin structures. We explore the pharmacological profiles of various coumarin derivatives, including their anti-cancer, anti-inflammatory, antiviral, antioxidant, antibacterial, and anti-tuberculosis activities, among others. The review examines how the incorporation of different functional groups on the coumarin scaffold can modulate its effectiveness against various diseases, particularly cancer. Furthermore, we discuss promising results from coumarin-based hybrids, such as coumarinpyridine, coumarin-uracil, and coumarin-quinoline derivatives, demonstrating their efficacy against a range of pathogens. This comprehensive overview serves as a valuable resource for researchers interested in the potential of coumarin derivatives in therapeutic applications.

Organotin(IV) complexes of tridentate (ONO) hydrazone ligands: synthesis, spectral characterization, antituberculosis, antimicrobial, anti-inflammatory, molecular docking and cytotoxicity studies.

Infectious diseases have a significant impact in the historical trajectory of humanity, exerting profound influence on societies, driving advancements in medical science, and significantly impacting individuals on a worldwide scale. Consequently, this research endeavours to identify potent agents combatting tuberculosis, inflammation, and microbial deformities. The investigation focuses on hydrazones (1,2) endowed eight organotin(IV) complexes, where hydrazones were derived from 2-acetyl-1H-indene-1,3(2H)-dione and 2-phenoxypropanehydrazide/2-(2,4-dichlorophenoxy)propanehydrazide. All compounds underwent thorough characterization utilizing a variety of spectral and analytical techniques including, multinuclear NMR, FT-IR, HRMS, UV-Vis, SEM-EDAX, TGA, XRD, molar conductance measurements, establishing the pentacoordinated environment around tin(IV) ion with tridentate (ONO) mode of chelation of hydrazones. Powder XRD revealed the ligand's crystalline and complexes' semi-crystalline nature, while thermal analysis indicated two-step decomposition leaving tin oxide residue. In vitro evaluations utilize microplate alamar blue assay for assessing anti-tuberculosis activity, serial dilution technique for antimicrobial efficacy, and bovine serum albumin method for evaluating anti-inflammatory properties. The complexes exhibited higher biological activities than their respective ligands and the activity of the complexes follow the order: Ph2SnL1-2 > Bu2SnL1-2 > Et2SnL1-2 > Me2SnL1-2. Among them, phenyl complex (10) [Ph2SnL2] displays superior efficacy against TB dysfunction (MIC: 0.0180 ± 0.009μmol/mL) and also demonstrates exceptional potency in combating inflammation (IC50: 7.27 ± 0.04μM), and microbial (MIC: 0.0045μmol/mL) infections, comparable to standard drugs. Additionally, cytotoxicity testing against vero cell line revealed decreased toxicity at lower concentrations, and attenuated by chelation. Phenyl complex (10) [Ph2SnL2] shows promising cytotoxicity at 3.12µg/mL (19.29 ± 0.09%). Further, The diphenyltin(IV) complex (10), identified as the most effective against TB, shows stronger binding to key 3PTY protein residues (-42.2kJ/mol) compared to ligand (2) (-33.4kJ/mol), correlating with its superior anti-tuberculosis potency in biological assays. This comprehensive approach aims to actively contribute to ongoing initiatives addressing infectious diseases, thereby advancing global health and overall well-being.

Ni(II)-selenosemicarbazones complexes as promising anticancer and anti-tubercular agents: Synthesis, characterization, molecular docking and binding studies with HSA and ct-DNA

Reaction of nickel(II) acetate with selenosemicarbazones (2-HOxsesc, 3-MeHOxsesc, 6-ClHOxsesc, 3-HIndsesc, 3-AcHIndsesc, 9-HAnsesc, 1-HNapsesc, 2-HNapsesc) in 1:2 (M:L) molar ratio yielded complexes of formula, [Ni(sesc)2] 1–8 (sesc = 2-Oxsesc 1, 3-MeOxsesc 2, 6-ClOxsesc 3, 3-Indsesc 4, 3-AcIndsesc 5, 9-Ansesc 6, 1-Napsesc 7, 2-Napsesc 8).Complexes are characterized using elemental analysis, FTIR, NMR (1H and 13C) spectroscopy and Mass spectrometry. The full optimized energy for 2-HOxsesc and its complex was found through Density Functional Theory calculation using B3LYP level and predicted geometry parameters are compared with literature. Selenosemicarbazones and their complexes were tested for their anti-tuberculosis activity against M. tuberculosis H37RV strain and anticancer activity against PA-1 and DU145cell lines. The anti-TB activity of 3-AcHIndsesc (MIC = 25 μg/mL) got exceptionally enhanced on complexation with Ni(II) (complex 5, MIC = 0.8 μg/mL). Anticancer activity of ligands have got enhanced on complexation with Ni(II) metal ion and best results were obtained in case of complex 5 (PA-1, IC50 =1.28; DU145, IC50 =3.83). The binding constant of 6.5 × 103M-1 and 3 × 104M−1 obtained from absorption spectroscopy (UV–Vis) indicates strong binding of complex 5 with HSA and ct-DNA. The molecular interaction of 3-AcHIndsesc and complex 5 with mycobacterium tuberculosis enoyl reductase and DNA (PDB ID: 1BNA) were checked with docking studies. The docking studies with mycobacterium tuberculosis enoyl reductase and DNA (PDB ID: 1BNA) gave minimum binding energy of -8.9 Kcal/mol and -7.5 Kcal/mol respectively for complex 5. The docking results are in well agreement with experimental data.

3,5-disubstituted pyridines with potent activity against drug-resistant Mycobacterium tuberculosis clinical isolates.

Aim: We designed and synthesized a series of compounds with a 3,5-disubstituted pyridine moiety and evaluated them against Mycobacterium tuberculosis (Mtb) and drug-resistant Mtb clinical isolates.Methodology: A library of 3,5-disubstituted pyridine was synthesized. The compounds were screened for activity against M. tuberculosis H37Rv. The optimal substitutions needed for the activity were identified through structure-activity relationship (SAR) studies.Results: From the screening studies, compounds 24 and 26 were identified as potent members of this series with Minimum Inhibitory Concentration (MIC) of 1.56μg/ml against M. tuberculosis H37Rv. These compounds did not show any inhibition against a panel of ESKAPE pathogens at >50μg/ml indicating their selective killing of M. tuberculosis H37Rv. Importantly, compound 24 showed a selectivity index of 54.64 against CHO-K1 and 78.26 against VERO cell lines, while compound 26 showed a selectivity index of 108.5 against CHO-K1 and 63.2 against VERO cell lines, respectively. Compound 24 formed a stable complex with the target protein DprE1 with predicted binding energy -8.73kcal/mol and inhibited multidrug-resistant clinical isolate of M. tuberculosis at 6.25μg/ml.Conclusion: This study identified the 3,5-disubstituted pyridine derivative 24 with potent antituberculosis activity and can be taken forward to generate new preclinical candidate.

Synthesis, physicochemical characterisation of novel Azo-2-{[(E)-{2-hydroxy-3-methoxy-5-[(E)-(4-nitrophenyl)diazenyl]phenyl}methylidene]amino}pyridin-3-ol and its metal complexes; evaluation of anti-diabetic, anti-tuberculosis, DFT, Docking and Electrochemical detection of pain relief Paracetamol

A azo-dye Schiff base 2-{[(E)-{2-hydroxy-3-methoxy-5-[(E)-(4-nitrophenyl)diazenyl]phenyl}methylidene]amino}pyridin-3-ol (HMNP) and its metal complexes. viz., [M(HMNP)2], [M= Co2+, Ni2+ and Cu2+] were synthesised and characterised by physicochemical techniques. All data suggest that the HMNP is tridentate ligand and its metal complexes have octahedral geometry. The optimized chemical parameters evaluated using DFT studies. Molecular docking has been performed by mycobacterium tuberculosis Enoyl-Acyl Carrier Protein Reductase (InhA) receptor to predict the binding affinity. The [Cu(HMNP)2] exhibited binding energy of -292.12 kcal/mol. In vitro antidiabitic and anti-tuberculosis activity showed that the complexes exhibited promising growth inhibition with effective IC50 potency values. Recent diagnoses about diabetes, tubercular and covid-19 patients have shown respiratory tract and inflammatory infections. In such patients paracetamol improve the resistance against infections. In this connection, electrochemical detection of paracetamol by a glassy carbon electrode modified using [Co(HMNP)2]. The analytical profile of [Co(HMNP)2]/GCE showed that the LOD of paracetamol (0.166 and 0.133 µM/L) linear range are (0.5-8 and 0.4-45 µM/L) and sensitivity is (0.451 and 6.452 μAμM−1cm-2) which were investigated by both CV and DPV technique's. Further, the prepared sensor, [Co(HMNP)2]/GCE has more stability and showed less leaching property.

Tetrabutylammonium Hydrogen Sulfate (TBAHS) Catalyzed Microwave-Assisted Synthesis of 3,4,5,6,7,9-Hexahydro-1H-xanthene-1,8-(2H)-dione Derivatives and its Biological Study

In this study, a facile and eco-friendly synthesis of novel 3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)-dione derivatives using tetrabutylammonium hydrogen sulfate (TBAHS) as a catalyst in the microwave reactor is presented. The reaction involved the condensation of aromatic aldehydes with 1,3-cyclohexanedione in ethanol as solvent, offering significant advantages in terms of reaction rate, yield and purity. The use of TBAHS as catalyst in conjunction with microwave irradiation facilitated the formation of the target xanthene derivatives in remarkably short reaction times. Moreover, Monowave 50 microwave reactor provided precise control over reaction parameters, enabling rapid optimization of reaction conditions. Further these synthesized compounds were systematically evaluated for their antibacterial, antituberculosis and antioxidant activities.

Exploration of newly synthesized transition metal(II) complexes for infectious diseases.

Aim: In the annals of human history, infectious diseases significantly influencing the collective well-being of people worldwide. Consequently, to identify effective agents for infectious ailments, the octahedral Co(II), Ni(II), Cu(II), Zn(II) complexes of 4-(3-methoxyphenyl)pyrimidin-2-amine and 2-methoxy-1-napthaldehyde based ligand were synthesized and well characterized in the current investigation.Results & methodology: The synthesized compounds were evaluated for anti-TB, anti-inflammatory, antibacterial, antifungal activities by microplate Alamar blue, bovine serum albumin, serial dilution assays. The [Zn(L1)2(H2O)2] complex (5) demonstrates robust potency with 0.0040±0.0007 and 0.0038μmol/ml MIC value in anti-tuberculosis and antimicrobial activities, correspondingly while 06.57±0.03μM IC50 value in anti-inflammatory investigation.Conclusion: Complex (5) show promising potential as targets for pathogen deformities, supported by rigorous biological and computational investigations including pharmacophore modelling, molecular docking (binding score -121.018 and -59.8662kcal/mol for 6H53 and 1CX2 proteins, respectively), DFT (Density functional theory), MESP (MolecularElectrostaticPotential) and ADMET (absorption, distribution, metabolism, excretion and toxicity).

Synthesis and characterization of hydrazone derivative and its antibacterial, antifungal, antimalarial and antituberculosis activity studies

Synthesis and characterization of hydrazone derivative and its antibacterial, antifungal, antimalarial and antituberculosis activity studies

Biological Properties, Health Benefits and Semisynthetic Derivatives of Edible Astraeus Mushrooms (Diplocystidiaceae): A Comprehensive Review.

Edible Astraeus mushrooms are known for their nutritional and culinary benefits and potential therapeutic properties. However, more investigation and discussion are still needed to understand their mechanisms of action regarding observed biological activities and thorough chemical analysis of bioactive compounds. This review provides a comprehensive summary and discussion of the bioactive properties and mode of action of Astraeus extracts and their isolated compounds. It covers their reported antioxidant, anti-inflammatory, antidiabetic, anticancer, anti-tuberculosis, antimalarial, antiviral and antileishmanial activities, as well as their potential benefits on metabolic and cardiovascular health and immune function. The review highlights the significance of the biological potential of isolated compounds, such as sugar alcohols, polysaccharides, steroids, and lanostane triterpenoids. Moreover, the review identifies under-researched areas, such as the chemical analysis of Astraeus species, which holds immense research potential. Ultimately, the review aims to inspire further research on the nutraceuticals or therapeutics of these mushrooms.

The synthesis of 1-oxa-9-azaspiro[5.5]undecane derivatives and optimization of antituberculosis activity thereof

The synthesis of 1-oxa-9-azaspiro[5.5]undecane derivatives and optimization of antituberculosis activity thereof

A Robust In Vitro Anti‐tuberculosis, Antimicrobial, and Anti‐inflammatory Activities Based on Azomethine Chelates Incorporating Co(II), Ni (II), Cu(II), and Zn(II) Ions: Synthesis, Characterization, and Investigation of the Aspects of Docking Interaction

ABSTRACTIn recent times, there has been a growing exploration of transition metal complexes as potential solutions for significant health challenges, including tuberculosis, microbes infection, and inflammation. Therefore, in our ongoing effort to identify biologically effective agents, Co(II), Ni(II), Cu(II), and Zn(II) metal complexes of H2L1–H2L2 hydrazone ligands were synthesized. The structural features of synthesized compounds were recognized by employing several techniques such as FT‐IR, 1H NMR, 13C NMR, powder x‐ray diffraction (XRD), UV‐Vis, ESR, TG‐DTA, mass spectrometry, and molar conductance measurements. The bonding of ligands via Ophenolic, Oenolic, and Nazomethine donor atoms and the attachment of the three water molecules with metal ion to form the octahedral structure of complexes were corroborated by different spectroscopic techniques. The anti‐tuberculosis, antimicrobial, and anti‐inflammatory activities of the synthesized compounds were assessed using the microplate alamar blue assay, serial dilution, and bovine serum albumin (BSA) methods, respectively, and highlighted the more potency of the complexes than ligands. The synthesized Cu(II) (9) and Zn(II) (10) metal complexes exhibited excellent ability to inhibit the growth of H37Rv strain of Mycobacterium tuberculosis in comparison to standard drug streptomycin. The Cu(II) (6 and 9) and Zn(II) (10) complexes showed superb ability as antimicrobial agents, whereas Cu(II) (5) and Zn(II) (6) complexes exhibited significant anti‐inflammatory ability. The in vitro findings on the antituberculosis activity were reinforced by a significant molecular docking study, which has become a crucial component of computational research utilizing the enzyme Mtb Pks13 thioesterase domain of M. tuberculosis. Additionally, in this research work, the absorption–distribution–metabolism–excretion–toxicity (ADMET) study sparked the compounds' drug‐like behavior.

Attenuation of Quorum Sensing Mediated Virulence Factors and Biofilm Formation in Pseudomonas Aeruginosa PAO1 by Substituted Chalcones and Flavonols.

Flavonoids epitomize structural scaffolds in many biologically active synthetic and natural compounds. They showcase a diverse spectrum of biological activities including anticancer, antidiabetic, antituberculosis, antimalarial, and antibiofilm activities. The antibiofilm activity of a series of new chalcones and flavonols against clinically significant Pseudomonas aeruginosa PAO1 strain was studied. Antivirulence activities were screened by analysing the effect of compounds on the production of virulence factors like pyocyanin, LasA protease, cell surface hydrophobicity, and rhamnolipid. The best ligands towards the quorum sensing proteins LasR, RhlR, and PqsR were recognised using a molecular docking study. The gene expression in P. aeruginosa after treatment with test compounds was evaluated on quorum sensing genes including rhlA, lasB, and pqsE. The antibiofilm potential of chalcones and flavonols was confirmed by the efficient reduction in the production of virulence factors and downregulation of gene expression.

Hydrazide–Hydrazones as Potential Antitubercular Agents: An Overview of the Literature (1999–2023)

AbstractHydrazide–hydrazone derivatives are prevalent in numerous bioactive compounds, showcasing a diverse array of biological effects including antibacterial, antitubercular, antifungal, anticancer, anti-inflammatory, anticonvulsant, antiviral, and antiprotozoal properties. Consequently, numerous medicinal chemists have undertaken the synthesis of various hydrazide–hydrazones, subjecting them to evaluation for their biological activities. Among these, antituberculosis activity stands out as a recurring focus in the scientific literature. This paper provides a comprehensive overview of research spanning the last 24 years (1999–2023), concentrating on the antituberculosis properties of hydrazide–hydrazone derivatives. The insights presented herein could serve as a valuable roadmap for the development of novel hydrazide–hydrazones with potential antimicrobial efficacy.

Antituberculosis, antimicrobial, antioxidant, cytotoxicity and anti-inflammatory activity of Schiff base derived from 2,3-diaminophenazine moiety and its metal(II) complexes: structural elucidation, computational aspects, and biological evaluation

Abstract Enticed by the present scenario of infectious diseases, four new Co(II), Ni(II), Cu(II), and Cd(II) complexes of Schiff base ligand were synthesized from 6,6′-((1E-1′E)(phenazine-2,3-dielbis(azanylidene)-bis-(methanylidene)-bis-(3-(diethylamino)phenol)) (H 2 L) to ascertain as effective drug for antituberculosis, anti-inflammatory, antioxidant, cytotoxic and antimicrobial activities. The organic ligand and its metal(II) complexes were characterized by numerous physical and spectroscopic methods, which showed that the complexes have a general formula, [ML], (where M = Co(II) (C1), Ni(II) (C2), Cu(II) (C3) and Cd(II) (C4)), for metal complexes have been proposed and have a square planar geometry, are amorphous in nature, and are thermally stable. Data highlight obtained from activity testing against tuberculosis, inflammation, and oxidants that all compounds are significantly active against these symptoms. Also, was to evaluate the effectiveness of various compounds against bacterial and fungal strains. Specifically, four bacterial strains (Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa) and two fungal strains (Aspergillus flavus and Candida albicans) were tested and compared to the results of some standard drugs. The results revealed that compound C4 was more effective against bacterial strains than the comparison standard drugs. In addition, C3 was found to be the most effective of the comparison antibiotics against fungi, while the other compounds showed moderate antifungal activity. Moreover, to support the vitro results, certain computational studies as molecular docking studies, DFT, MESP, and AMEDT were also conducted to confirm the effectiveness of an organic ligand and its complexes against tuberculosis. These studies revealed that C4 is the most effective against tuberculosis and has desirable effects such as absorption, no degradation and no hepatotoxicity, etc.

Structural reactions, green chemistry solvents, topology surface, electronic and biological studies of 4-(dihydroxymethyl) pyridine-2-carbonitrile – Anti-tuberculosis activity

Spectroscopic properties of 4-(dihydroxymethyl) pyridine-2-carbonitrile have been theoretically scrutinized using DFT technique utilizing B3LYP approach along with 6–311G++(d,p) basis set. Electronic-stability, electronic transitions, and distribution of charge within the molecule were analyzed using FMO and NBO analyses, which involve π*(C13–C14) to π*(C10–C15) transition, with a maximum stabilization energy of 212.33 kcal/mol, which ascertain the molecule's stability. Vibrational assignments for FT-IR and FT-Raman spectrum have been conducted using PED for identifying functional groups. Topological analyses such as ELF, LOL, and RDG provided a comprehensive understanding of the distribution of charged particles across each element within molecule, enabling the identification of electrophilic and nucleophilic sites. DMPC adheres to Lipinski's rule of five, indicating suitability for oral administration similar to other drugs. Investigations using molecular docking were performed to analyze the biological asset of the compound. Protein 6UCR demonstrated superior binding potency with a minimum binding-energy reaching −8.5 kcal/mol, revealing its potential treatment for tuberculosis.

Treatment Related Factors Associated with Non-adherence to Anti-Tuberculosis Treatment

Background: Non-adherence to anti-tuberculosis treatment may result in persistent infectiousness on the part of the patient and a higher rate of treatment failure, relapse and drug resistance and therefore, is a significant barrier to the success in tuberculosis control. Objective: To determine the treatment related factors associated with non-adherence to anti-tuberculosis treatment among tuberculosis patients. Materials and method: This case control study was carried out among purposively selected 47tuberculosis patients non-adherent to treatment (cases) and 94 tuberculosis patients adherent to treatment (controls) and were interviewed with a semi-structured questionnaire and checklist in selected DOTS centres of Dhaka city. Results: Statistical analysis shows that, factors like delay in seeking tuberculosis treatment for >6 weeks (OR=4.57; 95% CI, 1.48-14.1) and getting medicine weekly once (OR=2.8; 95% CI, 1.13-6.77) were more likely to be associated with non-adherence to treatment. Lessfrequent visit by health providers (p=0.02), no support for side effect (p=0.042) and non-observation of medication (p=0.009) were also found significant. The reasons behind missing anti-TB doses among non-adherent cases were due to feeling better (53.2%), personal reason (25.5%), feeling worse (19.1%) and forgot to take medicine (2.2%). Conclusion: Mass awareness among the tuberculosis patients is required to improve attitude towards anti-tuberculosis treatment and activities of tuberculosis control programme require further strengthening especially in targeting the patients of low economic status. Delta Med Col J. Jan 2021;9(2): 96-100

Design, synthesis, and anti-mycobacterial evaluation of 1,8-naphthyridine-3-carbonitrile analogues.

Twenty-eight compounds, viz., 1,8-naphthyridine-3-carbonitrile (ANC and ANA) derivatives, were designed and synthesized through a molecular hybridization approach. The structures of these compounds were analyzed and confirmed using 1H NMR, 13C NMR, LCMS, and elemental analyses. The synthesized compounds were evaluated by in vitro testing for their effectiveness against tuberculosis using the MABA assay, targeting the Mycobacterium tuberculosis H37Rv strain. Their minimum inhibitory concentration (MIC) was determined, showing that the tested compounds' MIC values ranged from 6.25 to ≤50 μg mL-1. Among the derivatives studied, ANA-12 demonstrated prominent anti-tuberculosis activity with a MIC of 6.25 μg mL-1. Compounds ANC-2, ANA-1, ANA 6-8, and ANA-10 displayed moderate to good anti-tuberculosis activity with MIC values of 12.5 μg mL-1. Compounds with MIC ≤ 12.5 μg mL-1 were screened against human embryonic kidney cells to assess their potential cytotoxicity. Interestingly, these compounds showed less toxicity towards normal cells, with a selectivity index value ≥ 11. To further evaluate the binding pattern in the active site of enoyl-ACP reductase (InhA) from Mtb (PDB-4TZK), a molecular docking analysis of compound ANA-12 was performed using the glide module of Schrodinger software. The stability, confirmation, and intermolecular interactions of the cocrystal ligand and the highly active compound ANA-12 on the chosen target protein were investigated through molecular dynamics simulations lasting 100 ns. In silico predictions were utilized to assess the ADMET properties of the final compounds. A suitable single crystal was developed and analyzed for compound ANA-5 to gain a deeper understanding of the compounds' structures.

Anti-tuberculosis effect of microbiome therapeutic PMC205 in extensively drug-resistant pulmonary tuberculosis in vivo

BackgroundTuberculosis is a highly contagious disease caused by Mycobacterium tuberculosis, and the increase in antibiotic resistance threatens humankind. Therefore, there is an urgent need to develop new anti-tuberculosis drugs that can overcome the limitations of existing drugs. Here, we report the anti-tuberculosis effect of microbiome therapeutic PMC205, a strain of Bacillus subtilis. MethodsThe anti-tuberculosis activity of probiotics was evaluated in mouse models of lethal and latent pulmonary tuberculosis induced by high or low-dose infection of the extensively drug-resistant strain. Probiotics were administered by inhalation, and the burden of M. tuberculosis in the lungs, along with mortality and clinical observations, were monitored for 12 weeks and 8 months, respectively. For an in-depth understanding, analysis of the microbiome and inflammatory profile of the lung microenvironment and induction of autophagy in vitro were explored. ResultsAfter inhalation administration of PMC205 for 3 months, the survival rate was 100%, unlike all deaths in the saline-treated group, and the burden of M. tuberculosis in the lungs was reduced by log 1.3 in the 8-month latent tuberculosis model. Moreover, PMC205 induced recovery of disrupted lung microflora, increased butyric acid, and suppressed excessive inflammation. It also promoted autophagy. ConclusionsThese results confirm PMC205’s anti-tuberculosis effect, suggesting that it can be developed as an adjuvant to current antibiotic therapy to solve the drug-resistant tuberculosis problem.

Marine Pharmacology in 2019-2021: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action.

The current 2019-2021 marine pharmacology literature review provides a continuation of previous reviews covering the period 1998 to 2018. Preclinical marine pharmacology research during 2019-2021 was published by researchers in 42 countries and contributed novel mechanism-of-action pharmacology for 171 structurally characterized marine compounds. The peer-reviewed marine natural product pharmacology literature reported antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral mechanism-of-action studies for 49 compounds, 87 compounds with antidiabetic and anti-inflammatory activities that also affected the immune and nervous system, while another group of 51 compounds demonstrated novel miscellaneous mechanisms of action, which upon further investigation, may contribute to several pharmacological classes. Thus, in 2019-2021, a very active preclinical marine natural product pharmacology pipeline provided novel mechanisms of action as well as new lead chemistry for the clinical marine pharmaceutical pipeline targeting the therapy of several disease categories.