This report describes a case of liver hilar tuberculous lymphadenitis complicated by biliary stricture, diagnosed with endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). A 44-year-old woman was referred to our center for further evaluation of abnormal liver function tests. Abdominal ultrasound/contrast-enhanced computed tomography (CT) revealed a 15-mm hypovascular mass with a weakly enhanced margin at the liver hilum. Magnetic resonance cholangiopancreatography revealed dilatation of the intrahepatic bile ducts in the left lobe of liver and gradual narrowing of the left hepatic duct. Biliary stricture associated with enlarged hilar lymph nodes due to metastasis or malignant lymphoma was suspected, but calcification on chest CT and a positive T-SPOT test did not rule out tuberculosis. After transpapillary brush cytology of the bile duct stricture failed to confirm the diagnosis, EUS-FNA of hilar lymph nodes was performed and showed positive for the acid-fast bacillus and polymerase chain reaction for Mycobacterium tuberculosis DNA as well as epithelioid granulomas on pathological evaluation. Those findings led to a diagnosis of hilar tuberculous lymphadenitis. The patient is under treatment with antituberculosis drugs. Abdominal tuberculous lymphadenitis is rare and some cases diagnosed as lymphadenopathy of unknown origin have required surgery. EUS-FNA is a safe and minimally invasive diagnostic method in such cases.

The current study explores the antimycobacterial efficacy of lichen-derived psoromic acid (PA) against clinical strains of Mycobacterium tuberculosis (M.tb). Additionally, the inhibitory efficacy of PA against two critical enzymes associated with M.tb, namely, UDP-galactopyranose mutase (UGM) and arylamine-N-acetyltransferase (TBNAT), as drug targets for antituberculosis therapy were determined. PA showed a profound inhibitory effect towards all the M.tb strains tested, with minimum inhibitory concentrations (MICs) ranging between 3.2 and 4.1 µM, and selectivity indices (SIs) ranging between 18.3 and 23.4. On the other hand, the standard drug isoniazid (INH) displayed comparably high MIC values (varying from 5.4 to 5.8 µM) as well as low SI values (13.0⁻13.9). Interestingly, PA did not exhibit any cytotoxic effects on a human liver hepatocellular carcinoma cell line even at the highest concentration tested (75 µM). PA demonstrated remarkable suppressing propensity against UGM compared to standard uridine-5'-diphosphate (UDP), with 85.8 and 99.3% of inhibition, respectively. In addition, PA also exerted phenomenal inhibitory efficacy (half maximal inhibitory concentration (IC50) value = 8.7 µM, and 77.4% inhibition) against TBNAT compared with standard INH (IC50 value = 6.2 µM and 96.3% inhibition). Furthermore, in silico analysis validated the outcomes of in vitro assays, as the molecular interactions of PA with the active sites of UGM and TBNAT were unveiled using molecular docking and structure⁻activity relationship studies. Concomitantly, our findings present PA as an effective and safe natural drug plausible for use in controlling tuberculosis infections.

Tuberculosis is an ever-evolving infectious disease that urgently needs new drugs. In the search for new antituberculosis agents, a library of 3-cinnamoyl-4-hydroxy-6-methyl-2H-pyran-2-ones (CHPs) (2a-2y) was synthesized and evaluated against a standard virulent laboratory strain of Mycobacterium tuberculosis H37Rv. Out of 25 compounds, 11, 5, 7 and 2 (2a and 2u) showed least, moderate, good and appreciable activities, respectively, based on minimum inhibitory concentrations (MICs). Both 2a and 2u exhibited an MIC value of 4 μg ml-1, which was close to those of standard antituberculosis drugs ethambutol, streptomycin and levofloxacin. Neither 2a nor 2u showed any activity against Gram-positive or Gram-negative bacteria and even against non-tuberculous mycobacterium, i.e. Mycobacterium smegmatis. Thus, like the antituberculosis drugs rifampicin, isoniazid and pretomanid, they are highly TB specific. All the pyrone-based chalcones showed no recognizable level of cytotoxicity against normal human kidney cell line (HEK-293) up to 80 μM concentration and 11 exhibited an IC50 ≤ 100 μM (highest tested concentration). On further investigation, both 2a and 2u proved to be nontoxic against four human cell lines but 2a proved to be a better choice as it did not reach IC50 even at 100 μM (highest tested concentration) while the IC50 of 2u was around 80 μM. In conclusion, our results demonstrate that 2a is specific against M. tuberculosis with no appreciable toxicity; its activity matches that of some clinically approved antituberculosis drugs and it therefore merits further evaluation.

The present study utilised whole cell based phenotypic screening of thousands of diverse small molecules against Mycobacterium tuberculosis H37Rv (M. tuberculosis) and identified the cyclohexane-1,3-dione-based structures 5 and 6 as hits. The selected hit molecules were used for further synthesis and a library of 37 compounds under four families was synthesized for lead generation. Evaluation of the library against M. tuberculosis lead to the identification of three lead antituberculosis agents (37, 39 and 41). The most potential compound, 2-(((2-hydroxyphenyl)amino)methylene)-5,5-dimethylcyclohexane-1,3-dione (39) showed an MIC of 2.5 μg mL-1, which falls in the range of MICs values found for the known antituberculosis drugs ethambutol, streptomycin and levofloxacin. Additionally, this compound proved to be non-toxic (<20% inhibition at 50 μM concentration) against four human cell lines. Like first line antituberculosis drugs (isoniazid, rifampicin and pyrazinamide) this compound lacks activity against general Gram positive and Gram negative bacteria and even against M. smegmatis; thereby reflecting its highly specific antituberculosis activity.