Nephrotoxicity, the rapid impairment of kidney function caused by harmful drugs and chemicals, affects about 20% of cases and is projected to become a leading cause of death by reactive oxygen species (ROS). Gentamicin (GM), an aminoglycoside antibiotic is one of the well know drugs/chemicals to cause nephrotoxicity both in humans and animals. A study on the effects of a synthetic phenolic compound, called 5-a, on GM-induced nephrotoxicity in male Wistar albino rats was conducted. The rats were grouped into five groups: normal control (NC), GM control (GM), positive control (GM + Dexa), treatment I (GM + 5-a 5 mg/kg) and treatment II (GM + 5-a 10 mg/kg). Throughout the experiment, the rats’ weights were monitored, and at its conclusion, their serum and kidney tissues were analyzed for renal function indicators and inflammatory markers. The study also included histopathological evaluations, molecular docking studies, blood and urine analyses for electrolyte changes, and behavioural assessments for central nervous system impact. 2-{5-[(2-hydroxyethyl)-sulfanyl]-1,3,4-oxadiazol-2-yl} phenol (5-a) significantly protected against renal damage by reducing inflammatory markers, improving antioxidant defences, and decreasing kidney injury, particularly at higher doses. The findings suggest that compound 5-a, due to its anti-inflammatory and antioxidant properties, could be a promising therapeutic option for reducing gentamicin-induced nephrotoxicity and potentially for other kidney disorders in the future. These findings highlight the therapeutic effects of compound 5-a in alleviating gentamicin-induced nephrotoxicity.
Multidrug resistance and infectious disease have enormous spread despite drug discovery and development advancements. 1, 2, 4 -triazoles have been extensively studied, playing an imperative role in many pathologic conditions. A series of Schiff base triazoles; derived from Indole -3- acetic acid with substituted Benzaldehydes (5a-5g) were designed, synthesized, and evaluated through various Spectroanalytical techniques. SwissADME was used to assess physicochemical properties and pharmacokinetic drug-likeliness behavior. (5a-5g) were evaluated for their varied biological potential through antioxidant, antimicrobial, enzyme inhibition, and cytotoxic evaluation. Schiff bases express drug-like nature as they follow Lipinski’s rule of five. 5b showed good antioxidant potential in total antioxidant capacity (TAC) and total reducing power (TRP) assays and was most active in the library in % free radical scavenging assay (%FRSA), showing 32% inhibition at 50 μg/mL concentration. Compounds showed antibacterial activity against various tested strains. 5e and 5f showed a minimum inhibitory concentration (MIC) value of 3.12 μg/mL for P.aeruginosa and K.pneumoniae, respectively. In the antifungal assay, only 5e inhibited one strain with a zone of inhibition >6 mm. These synthetic molecules possess good cytotoxic potential in the Brine Shrimp Lethality screening; 5c, 5d, and 5f exhibited LC50 =5.7 μg/mL. In the protein kinase inhibition assay, 5a, 5b, and 5g demonstrated inhibitory potential, showcasing the zone of inhibition as 7.5–10.5 mm for the bald one and 6–7.5 for the clear zone. These findings suggest that the compounds have antibacterial and cytotoxic potential, and there is a chance for further research and development in this area.
11 December 2024 in Journal of Biochemical and Molecular Toxicology