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Tuberculosis (TB) treatment faces significant challenges due to prolonged therapy and drug resistance, necessitating innovative anti-TB strategies. Thus, developing an innovative platform with effective anti-TB activity would offer more advantages. In this study, the pH-sensitive niosomal formulation of lactoferricin (Lfcin-Nio) was fabricated using a microfluidic system. The optimization of Lfcin-Nio formulation was statistically carried out based on the Central Composite Design (CCD). The desirable properties of Lfcin-Nio were achieved with a small particle size (171.68 ± 0.97 nm), a narrow polydispersity index; PDI (0.24 ± 0.002), an acceptable zeta potential; ZP (− 69.86 ± 0.64 mV), and high entrapment efficiency; %EE (75.59 ± 2.78%) with a prediction error of less than 5%. Lfcin-Nio demonstrated low cytotoxicity and stability for 28 days at room temperature and 4 °C. Lfcin-Nio also had a release profile in response to acidic pH, with approximately 50%, 70%, and 80% cumulative release at pH 7.4, 6.5, and 5.5, respectively, within the first 6 h. Notably, Lfcin-Nio exhibited enhanced anti-mycobacterial activity against both extracellular and intracellular Mycobacterium tuberculosis (Mtb), requiring a lower concentration for intracellular Mtb attenuation. Proteomic analysis revealed that Lfcin-Nio modulated immune response-related proteins, including complement C6 activation and suppression of inflammatory mediators. These findings suggest that Lfcin-Nio represents a promising anti-TB agent and further applies as a potential advancement in TB therapy.

Five new nucleoside antibiotics, named streptcytosines A–E (1–5), and six known compounds, de-amosaminyl-cytosamine (6), plicacetin (7), bamicetin (8), amicetin (9), collismycin B (10), and SF2738 C (11), were isolated from a culture broth of Streptomyces sp. TPU1236A collected in Okinawa, Japan. The structures of new compounds were elucidated on the basis of their spectroscopic data (HRFABMS, IR, UV, and 2D NMR experiments including 1H-1H COSY, HMQC, HMBC, and NOESY spectra). Streptcytosine A (1) belonged to the amicetin group antibiotics, and streptcytosines B–E (2–5) were derivatives of de-amosaminyl-cytosamine (6), 2,3,6-trideoxyglucopyranosyl cytosine. Compound 1 inhibited the growth of Mycobacterium smegmatis (MIC = 32 µg/mL), while compounds 2–5 were not active at 50 µg/disc. Bamicetin (8) and amicetin (9) showed the MICs of 16 and 8 µg/mL, respectively.

Mycobacterium abscessus subsp. massiliense (Mabs) causes chronic infections, which has led to the need for new antimycobacterial agents. In this study, we investigated the antimycobacterial and anti-inflammatory activities of the ethyl acetate fraction of Bixa orellana leaves (BoEA) and ellagic acid (ElAc). In silico analysis predicted that ElAc had low toxicity, was not mutagenic or carcinogenic, and had antimicrobial and anti-inflammatory activities. Apparently, ElAc can interact with COX2 and Dihydrofolate reductase (DHFR) enzymes, which could explain both activities. In vitro analysis showed that BoEA and ElAc exerted antimicrobial activity against Mabs (minimum inhibitory concentration of 1.56, 1.56 mg/mL and bactericidal concentration of 6.25, 3.12 mg/mL, respectively. Clarithromycin showed MIC and MBC of 1 and 6 µg/mL). Treatment with BoEA or ElAc increased survival of Tenebrio molitor larvae after lethal infection with Mabs and reduced carrageenan-induced paw edema in mice, around 40% of edema volume after the fourth hour, similarly to diclofenac. In conclusion, BoEA and ElAc exert antimicrobial effects against Mabs and have anti-inflammatory effects, making them potential sources of antimycobacterial drugs. The biological activities of ElAc may be due to its high binding affinities predicted for COX2 and DHFR enzymes.

The incidence of Mycobacterium marinum infection is on the rise; however, the existing drug treatment cycle is lengthy and often requires multi-drug combination. Therefore, there is a need to develop new and effective anti-M. marinum drugs. Cochliomycin A, a 14-membered resorcylic acid lactone with an acetonide group at C-5′ and C-6′, exhibits a wide range of antimicrobial, antimalarial, and antifouling activities. To further explore the effect of this structural change at C-5′ and C-6′ on this compound’s activity, we synthesized a series of compounds with a structure similar to that of cochliomycin A, bearing ketal groups at C-5′ and C-6′. The R/S configuration of the diastereoisomer at C-13′ was further determined through an NOE correlation analysis of CH3 or CH2 at the derivative C-13′ position and the H-5′ and H-6′ by means of a 1D NOE experiment. Further comparative 1H NMR analysis of diastereoisomers showed the difference in the chemical shift (δ) value of the diastereoisomers. The synthetic compounds were screened for their anti-microbial activities in vitro. Compounds 15–24 and 28–35 demonstrated promising activity against M. marinum, with MIC90 values ranging from 70 to 90 μM, closely approaching the MIC90 of isoniazid. The preliminary structure–activity relationships showed that the ketal groups with aromatic rings at C-5′ and C-6′ could enhance the inhibition of M. marinum. Further study demonstrated that compounds 23, 24, 29, and 30 had significant inhibitory effects on M. marinum and addictive effects with isoniazid and rifampicin. Its effective properties make it an important clue for future drug development toward combatting M. marinum resistance.

Background/Objectives: Nifuroxazide (Nfz) is a drug that has been used as a scaffold for designing antimicrobial and antiparasitic agents. This study aimed to synthesize and evaluate in vitro of Nfz and twenty-five 4-hydroxybenzhydrazone derivatives as potential anti-Trypanosoma cruzi, anti-Leishmania mexicana, and anti-Mycobacterium tuberculosis agents. Methods: The compounds were synthesized by condensing 4-hydroxybenzhydrazide with appropriate aldehydes in acidic conditions and structurally confirmed by spectroscopic techniques. All compounds were evaluated in vitro against T. cruzi strains (NINOA and A1), L. mexicana (M379 and FCQEPS strains), and M. tuberculosis (H37Rv strain), followed by enzymatic assays against T. cruzi cysteine proteases. Results: Compound Nfz-24 (IC50 = 6.8 μM) had better trypanocidal activity than the reference drugs benznidazole (IC50 > 30 μM) and nifurtimox (IC50 > 7 μM) against the NINOA strain, and Nfz-8 (IC50 = 7.2 μM) was the compound most active against the A1 strain with a high inhibition of T. cruzi cysteine proteases (IC50 = 4.6 μM) and low cytotoxic effects (CC50 >100 μM). On the other hand, compound Nfz-5 (IC50 = 5.2 μM) had a 25-fold better leishmanicidal effect than glucantime (IC50 > 125 μM) against the L. mexicana M379 strain, and compound Nfz-13 had the best leishmanicidal effects (IC50 = 10.2 μM) against the FCQEPS strain. Finally, Nfz, Nfz-1, and Nfz-2 had minimum inhibitory concentration (MIC) values of 12.3, 5.1, and 18.8 μg/mL against M. tuberculosis, respectively. Conclusions: In summary, these results suggest that the compounds Nfz-1, Nfz-2, Nfz-5, Nfz-8, Nfz-10, Nfz-15, Nfz-24, and Nfz-25 are candidates for further studies to develop new and more potent anti-T. cruzi, anti-leishmaniasis, and anti-M. tuberculosis agents.

A new aaptamine class alkaloid, designated 2-methoxy-3-oxoaaptamine (1), together with seven known aaptamines (2–8) were isolated from a marine sponge of Aaptos sp. as anti-mycobacterial substances against active and dormant bacilli. The chemical structure of 1 was determined on the basis of spectroscopic analysis. Compound 1 was anti-mycobacterial against Mycobacterium smegmatis in both active growing and dormancy-inducing hypoxic conditions with a minimum inhibitory concentration (MIC) of 6.25 μg/ml, and compounds 2, 5, 6, and 7 showed anti-mycobacterial activities under hypoxic condition selectively, with MIC values of 1.5–6.25 μg/ml.

Paul Farmer has battled AIDS in rural Haiti and deadly strains of drug-resistant tuberculosis in the slums of Peru. A physician-anthropologist with more than fifteen years in the field, Farmer writes from the front lines of the war against these modern plagues and shows why, even more than those of history, they target the poor. This \"peculiarly modern inequality\" that permeates AIDS, TB, malaria, and typhoid in the modern world, and that feeds emerging (or re-emerging) infectious diseases such as Ebola and cholera, is laid bare in Farmer's harrowing stories of sickness and suffering. Challenging the accepted methodologies of epidemiology and international health, he points out that most current explanatory strategies, from \"cost-effectiveness\" to patient \"noncompliance,\" inevitably lead to blaming the victims. In reality, larger forces, global as well as local, determine why some people are sick and others are shielded from risk. Yet this moving account is far from a hopeless inventory of insoluble problems. Farmer writes of what can be done in the face of seemingly overwhelming odds, by physicians determined to treat those in need. Infections and Inequalities weds meticulous scholarship with a passion for solutions—remedies for the plagues of the poor and the social maladies that have sustained them.