AIMS
To synthesize and evaluate a series of thiosemicarbazone derivatives (2a-2g) incorporating thiophene-2-carboxylic acid as urease inhibitors.
MATERIALS AND METHODS
The compounds were synthesized and characterized using modern spectroscopic techniques. In vitro urease inhibition was determined followed by computational analysis including docking, density functional theory (DFT), molecular dynamics simulations (MD), normal mode analysis (NMA), and SwissADME profiling. Compounds 2g, 2d, and 2b emerged as potent inhibitors with IC50 values of 5.48 ± 0.18 to 9.44 ± 0.32 µM, outperforming the reference thiourea (IC50 = 22.13 ± 2.82 µM). Structure-Activity Relationship (SAR) analysis revealed that electron-withdrawing nitro substituents at para positions dramatically enhanced inhibitory potency. Docking investigation demonstrated robust interactions with the urease active site that includes binuclear nickel center and residues His492, His519, and Asp633. DFT calculations established strong correlations between chemical reactivity indices and biological activity. Molecular docking and MD simulations validated stable binding interactions with key residues (His492, His519, and Asp633). NMA revealed enhanced flap flexibility (λ1 = 1.39 × 10-6) and motional coupling upon 2g binding.
CONCLUSION
These results expose the synthesized compounds, especially 2g as a potent urease inhibitor and provide a valuable insight for future anti-urease drug development.
W. Khan, Laiba, Imtiaz Ahmad et al.· Future Medicinal Chemistry· 0 citations
The growing prevalence of antimicrobial resistance and cancer has intensified interest in natural products as sources of biologically active compounds with potential pharmaceutical relevance. In this study, the phytochemical composition of the methanolic extract of Artemisia abyssinica aerial parts (MEAA) was comprehensively characterized using liquid chromatography–tandem mass spectrometry (LC–MS/MS) and gas chromatography–mass spectrometry (GC–MS), and its in vitro antimicrobial, antioxidant, cytotoxic, and molecular docking properties were evaluated. LC–MS/MS analysis revealed a diverse profile dominated by flavonoids and phenolic compounds, including myricetin, quercetin, apigenin derivatives, hispidulin, and taxifolin, while GC–MS analysis tentatively identified several non-polar constituents, with gitoxigenin as a putative major component. MEAA exhibited moderate antibacterial activity against Micrococcus luteus (inhibition zone 15 mm; MIC = 2 mg/mL) and moderate activity against Streptococcus pneumoniae and Escherichia coli. The extract demonstrated weak antioxidant activity in the DPPH assay (IC50 = 268.15 µg/mL) and moderate cytotoxicity against HepG-2 hepatocellular carcinoma cells (IC50 = 59.2 µg/mL) compared with Adriamycin (IC50 = 6.9 µg/mL). Molecular docking was employed to provide supportive structural insights, suggesting that selected flavonoids, particularly myricetin, apigenin, and hispidulin, may interact favorably with DNA gyrase, epidermal growth factor receptor, and urease. Overall, this study provides an analytical and biological profile of MEAA and highlights its phytochemical richness and early-stage bioactivity, supporting its relevance for further pharmaceutical investigation as well as its potential as a natural bioresource for future applications.
Abdu Aldarhami, Suliman A. Alderhami, Hassen Harzali et al.· Bioresources and Bioprocessi...· 0 citations
AIMS
Diabetes mellitus (DM) is a severe metabolic disease characterized by increased blood glucose levels due to reduced insulin action or secretion. This study aimed to synthesize new polyhydroquinoline (PHQ)-based acyl hydrazide derivatives and assess their potential as dual inhibitors of α-amylase and α-glucosidase enzymes.
MATERIALS AND METHODS
Various acyl hydrazide derivatives of PHQ were synthesized via a multi-step reaction and structurally deduced through modern spectroscopic techniques. These compounds were evaluated for their in vitro studies, while molecular docking was performed to gain mechanistic insights into their biological activities.
RESULTS AND DISCUSSION
In the series, compound (2c) emerged as the most potent inhibitor against both enzymes (IC50 = 0.44 ± 0.07 µM and 0.17 ± 0.01 µM, respectively), showing greater efficacy than acarbose. Density functional theory (DFT) analysis revealed valuable insights into the electronic properties and showed the best correlation with the biological targets. Moreover, molecular docking analysis showed good binding interactions with the active sites of both enzymes, which was supported by the experimental activities.
CONCLUSION
These integrated experimental and computational results demonstrate that the polyhydroquinoline scaffold represents a promising platform for developing next-generation antidiabetic therapeutics with enhanced efficacy and favorable safety profiles.
Sultan Muhammad, A. Latif, Aftab Alam et al.· Future Medicinal Chemistry· 0 citations