Current Issue : January-March Volume : 2026 Issue Number : 1 Articles : 5 Articles
The development of multifunctional drug delivery systems that integrate therapeutic and diagnostic capabilities remains a major challenge in oncology. In the present work we investigated hybrid carriers composed of human serum albumin and hemoglobin (HSAHb) for doxorubicin (DOX) delivery combined with radionuclide and fluorescence imaging. Using molecular docking simulations, we systematically evaluated the interactions of HSA-Hb assemblies with twelve technetium-99m (99mTc)-labeled radiopharmaceuticals, DOX, and four near-infrared (NIR) dyes. The results revealed that hemoglobin markedly expands the binding landscape, providing exclusive and high-affinity sites for several 99mTc complexes (notably TcMEB and TcDIS), while also serving as the primary scaffold for DOX and NIR dyes. Two distinct DOX-binding pockets were identified within Hb subunits, suggesting enhanced drug stability and potential responsiveness to tumor hypoxia. Fluorescent dyes, including methylene blue, indocyanine green, AK7-5, and SQ1, exhibited preferential binding to Hb with affinities higher than those observed for albumin, indicating superior suitability for optical imaging. Importantly, the partitioning of radiopharmaceuticals to albumin and therapeutic/imaging ligands to hemoglobin reduced binding competition and enabled the simultaneous integration of multimodal functions within a single construct. These findings highlight HSA-Hb nanocarriers as promising candidates for next-generation theranostic platforms, combining efficient DOX delivery with non-invasive radionuclide and fluorescence monitoring....
Monoacylglycerol lipase (MAGL) degrades the endocannabinoid 2-arachidonyl glycerol. MAGL inhibitors, such as the triterpene pristimerin, alleviate neuropathic pain in animal models. In silico studies were carried out using SwissDock, PyRx-0.8 and CB-Dock2, to check if they correlated with the in vitro MAGL inhibition potency of various triterpenes. In terms of affinity, free energy of binding and docking scores to MAGL, pristimerin (52.75, −9.32, −10.83, and −11.5 kcal/mol) was better than euphol (44.86, −8.49, −9.56, and −10.7 kcal/mol), which in turn was better than β-amyrin (35.17, −7.37, −8.21, and −8.8 kcal/mol). Finally, β-amyrin was better than or equal to α-amyrin (35.10, −7.19, −7.95, and −8.6 kcal/mol). In molecular dynamic simulations (MDSs), pristimerin exhibited the highest stability and reached the steady state after 20 ns with the lowest root mean square fluctuation (RMSF) at the binding site, compared to the triterpenes. The reported half maximal inhibitory concentration (IC50) values of recombinant human and rat MAGL inhibition were in the following order: α-amyrin > β-amyrin > euphol > pristimerin. Linear regression analysis showed that the affinity, free energy of binding, and docking scores significantly correlated with the IC50 of MAGL inhibition. Amongst the triterpenes studied, pristimerin was the most potent inhibitor of MAGL and also had the highest affinity in the in silico studies. Thus, molecular docking and MDS results correlated with the potency of triterpenes inhibiting MAGL activity in vitro and could be used for screening of triterpenes prior to experimental validation....
Neglected diseases significantly impact the world, and there is a lack of effective treatments, requiring therapeutic alternatives. Thus, the study of the phytochemical and schistosomicidal activity evaluation of Copaifera oblongifolia leaves’ crude extract was conducted. The quercitrin (1) and afzelin (2) were isolated from the crude extract. In the in vitro schistosomicidal activity test, the isolated compounds demonstrated promising results, with 75% mortality at a concentration of 12.5 μM after 72 h. Molecular docking calculations indicated that compounds 1 and 2 could potentially interact with the amino acids of the FAD binding site in the TGR enzyme, a crucial enzyme for the survival of Schistosoma mansoni. These interactions could have binding energies comparable to praziquantel, a preferred drug for treating schistosomiasis. Therefore, in silico and in vitro investigations are crucial for developing new studies that can reveal the antiparasitic potential of compounds of plant origin....
Due to their unique properties, small multitargeted drugs containing a fluorinated aromatic moiety and nitrogenous heterocycles are widely available on the market. Considering the pharmacological significance of organofluorine and heterocyclic compounds, in this study, we synthesized a series of pyrazoline derivatives (14−27) containing a pyrrolidine moiety and substituted them with a fluorine atom or a fluorine-containing (−CF3 or -OCF3) group at different positions. Also, the antidiabetic activities of new pyrazolines were screened by in vitro α-glucosidase and α-amylase activity assays in order to investigate their potential use in the treatment of Diabetes Mellitus, one of the most common and rapidly spreading diseases of today. The findings of this research indicated that compound 21, having a trifluoromethoxy group at the ortho position of the pyrrolidinebased pyrazolines at the phenyl ring, was determined to be the most effective α-glucosidase inhibitor with IC50 values of 52.79 ± 6.00 μM, compared to acarbose (IC50: 121.65 ± 0.50 μM). Molecular modeling studies demonstrated the high specificity of the most active pyrazoline−pyrrolidine hybrid molecules to the active site of α-glucosidase and their potential to exert inhibitory effects through various interactions with basic residues. Furthermore, molecular dynamics simulations provided comprehensive information about the structural properties and binding mechanisms of the complexes....
Antimicrobial resistance remains a major global public health challenge, contributing to increased mortality rate and treatment failures in an effort to address this growing challenge, the present research work focused on the synthesis and evaluation of new hydrazone scaffold and pyrazoline derivatives (coded HS6–HS10) as potential antimicrobial agents. The target compounds were synthesized via one-pot condensation reactions and characterized using FTIR, 1H, and 13C NMR techniques. Their antimicrobial activities were assessed in vitro against a panel of Gram-positive, Gram-negative bacteria, and fungal strains. However, their assessment revealed broad spectrum of antimicrobial activity, where the compounds bearing biaryl-substituted hydrazones with electron-donating or electron-withdrawing groups at para- and or meta-positions showed highest potency. However, MIC values of 12.5 mg/mL were observed against clinical isolates such as E. coli, S. typhi, and P. aeruginosa, while S. aureus, B. subtilis, and S. pneumoniae were inhibited at 12.5–25 mg/mL, while MIC values of 50 mg/mL were recorded against Aspergillus niger, indicating weak antifungal activity. The molecular docking studies conducted using target microbial enzymes such as dihydrofolate reductase (DHFR) and squalene epoxidase (SQLE) against the ligands HS7 and HS8 have strong binding affinities towards DHFR (− 9.6 and − 9.4 kcal/mol) and SQLE (− 9.8 and − 10.2 kcal/mol), respectively, outperforming standard reference drugs ciprofloxacin (− 7.4 kcal/mol) and terbinafine (− 9.8 kcal/mol). Meanwhile, the in silico ADME analysis confirmed that all compounds satisfied Lipinski’s rule of five, suggesting favourable drug-like properties. In conclusion, these findings suggest that substituted hydrazone and pyrazoline derivatives possess considerable promising scaffolds for developing better novel antimicrobial agents that are capable of combating resistant pathogens....
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