Novel isoxazole–triazole conjugates have been efficiently synthesized using 3-formylchromone as starting material according to a multi-step synthetic approach. The structures of the target conjugates and intermediate products were characterized by standard spectroscopic techniques (1H NMR and 13C NMR) and confirmed by mass spectrometry (MS). The all-synthesized compounds were screened for their antibacterial activity against three ATCC reference strains, namely Staphylococcus aureus ATCC 25923, Staphylococcus aureus ATCC BAA-44, and Escherichia coli ATCC 25922 as well as one strain isolated from the hospital environment Pseudomonas aeruginosa. The findings indicate that conjugate 7b exhibits a stronger antibacterial response against the tested Escherichia coli ATCC 25922 and Pseudomonas aeruginosa pathogenic strains compared to the standard antibiotics. Furthermore, hybrid compound 7b proved to have a bactericidal action on the Escherichia coli ATCC 25922 strain, as evidenced by the results of the MBC determination. Moreover, the ADMET pharmacokinetic characteristics revealed a favorable profile for the examined compound, as well as a good level of oral bioavailability. Molecular docking and molecular dynamics simulations were performed to explore the inhibition mechanism and binding energies of conjugate 7b with the proteins of Escherichia coli and Pseudomonas aeruginosa bacterial strains. The in silico results corroborated the data observed in the in vitro evaluation for compound 7b.
The plant Saussurea costus (Falc) Lipsch has many biological activities and a strong curative and preventive power against a variety of diseases including cancer, diabetes, and hemorrhoids. In the current study, phytochemical screening was carried out as well as an investigation of the antilithiatic and antioxidant activities of aqueous and ethanolic extracts of this plant. The results showed that aqueous and ethanolic extracts were effective in reducing cystine stone mass and that the aqueous extract of Saussurea costus (Falc) Lipsch had the highest percentage of dissolution (6.756 ± 1.024) (p < 0.05). A turbidimetric method and a crystallization test were used to evaluate the antilithiatic activity of an aqueous and ethanolic extract of this plant on calcium oxalate crystallization. The results of these methods revealed that the ethanolic extract of this plant has a significant inhibitory effect on calcium oxalate crystallization, with a percentage inhibition of (91.017 ± 0.299) (p < 0.05) for a concentration of 2 mg mL−1. The DPPH method revealed that the ethanolic extract of Saussurea costus (Falc) Lipsch with a concentration of (IC50 = 0.12325 mg mL−1) had the highest IC50, whereas the FRAP method revealed that the aqueous extract of Saussurea costus (Falc) Lipsch with a concentration of 300 µg mL−1 has the most significant reducing power with (OD = 0.56 ± 0.05). These findings indicate that aqueous and ethanolic extracts of Saussurea costus (Falc) Lipsch had a significant effect on whewellite and weddellite and a greater free radical scavenging effect but had no effect on cystine dissolution.
Saussurea costus (Falc) Lipsch is a traditional herb used to treat kidney stone problems because it contains several molecules used to treat this health problem, such as quercitrin. Infectious stones are the most painful of all urinary tract disorders, with ammonium phosphate (struvite) and carbapatite stones being the most common, caused by a bacterial infection with urease activity. These stones are treated with antibiotics, but antibiotic resistance is on the rise. The current study investigated the anti-urolithic activities of S. costus aqueous and ethanolic extracts of against struvite crystals synthesized using microscopic crystallization and turbidimetric methods, respectively. The utilized methods indicated that the ethanolic extract of this plant has a significant inhibitory effect on struvite crystallization, with a percentage inhibition of (87.45 ± 1.107) (p < 0.001) for a concentration of 1 mg mL−1 and a decrease in the number of struvite crystals, reaching values less than 100/mm3. For the number of struvite crystals inhibited by cystone, we found a value of 400/mm3 and with the aqueous extract we found 700/mm3. The antibacterial activity of the plant extracts studied was examined against several urease-producing bacteria, and this activity was evaluated by qualitative and quantitative evaluation methods; the highest minimum inhibitory concentration was seen in the ethanolic extract, with an MIC of 50 mg mL−1 for Staphylococcus aureus followed by an MIC of 200 mg mL−1 for Klebsiella pneumoniae. It showed a minimal bactericidal concentration (MBC) against S. aureus and K. pneumoniae (>50 mg mL−1 and >200 mg mL−1, respectively). Furthermore, to determine the extract’s anti-inflammatory activity, in vivo anti-inflammatory activity was investigated in rats. The results show that at a dose of 400 mg kg−1, the ethanolic extract has a maximum edema inhibition of 66%.
Phytotherapy, which involves the use of plant extracts and natural compounds for medicinal purposes, is indeed a promising alternative for managing urinary lithiasis. Many plants have been studied for their potential to prevent and treat kidney stones, and they may offer a more natural and potentially less harmful approach compared to conventional treatments. Additionally, phytotherapy may be more cost-effective. The aim of the present study was to investigate the antilithic potential of extracts and essential oils of Saussurea costus (Falc) Lipsch in two in vivo models, one on ethylene glycol-induced calcium oxalate crystal formation and the other to assess the effects of these extracts on magnesium oxide-induced struvite crystal formation. The experiment involved the administration of different doses of aqueous and ethanolic extracts of S. costus (200 and 400 mg/kg) and essential oils (25 and 50 mg/kg) to male Wistar rats, followed by the evaluation of various physiological, biochemical and histopathological parameters. The results demonstrated that the administration of S. costus essential oils and extracts had significant effects on the rats, influencing body weight, urine volume, crystal deposition, cytobacteriological examination of urine, and serum biochemical parameters. Histopathological examinations revealed varying impacts on the kidneys and livers of the treated rats. The findings suggest that S. costus extracts and essential oils may hold promise in inhibiting calcium oxalate crystal formation in vivo and influencing various physiological and biochemical parameters in rats. Overall, the 200 mg/kg ethanolic extract of S. costus demonstrated antilithiatic efficacy, did not exhibit signs of toxicity and reduced the number of crystals in the kidneys. Furthermore, the study did not find a significant effect on reducing struvite crystals.
This descriptive and exploratory observational case series examined intestinal colonisation and subsequent bacteraemia due to ESBL-producing Klebsiella pneumoniae (ESBL-Kp) in preterm neonates in Morocco. Prospective bacteriological cultures and antibiotic susceptibility testing were supported by phenotypic methods, including Brilliance ESBL Agar and the NG-Test CARBA-5 assay, for the rapid detection of ESBL and carbapenemase producers. Molecular analysis using PCR was also undertaken to identify specific resistance genes. A total of 567 rectal swabs were collected from 339 preterm neonates, yielding 293 K. pneumoniae isolates. ESBL-producing strains were identified in 53.6% of the neonates (182/339). Detected resistance genes included blaSHV (26.3%), blaCTX-M-1 (42.8%), blaTEM (30.2%), blaOXA-48 (50.0%), blaNDM(15.3%), and blaVIM (4.9%). Principal risk factors for colonisation were low birth weight (OR 1.69), very preterm birth (OR 6.24), enteral tube feeding (OR 2.02), and prolonged use of third-generation cephalosporins (OR 1.26). Among the neonates studied, 32 (9.4%) developed healthcare-associated bacteraemia, with 56.2% of these cases preceded by intestinal colonisation with ESBL-Kp. Clinically, severe respiratory distress and alveolar haemorrhage were strongly associated with increased mortality (aRR = 29.32 and 4.45, respectively). The findings highlight the clinical importance of early screening to guide infection control and antimicrobial stewardship in neonatal intensive care settings.