Current Issue : July-September Volume : 2026 Issue Number : 3 Articles : 5 Articles
This study focuses on the rational design and synthesis of new pyrrolidinone derivatives aimed at inhibiting the ACE2 receptor, a key entry point for SARS-CoV-2. Building on structural insights from known inhibitors like MLN-4760, five compounds featuring a pyrrolidinone core, with some incorporating indole rings, were synthesized and characterized. Their inhibitory activity against ACE2 was evaluated in vitro, with compound 4 showing the most promising results, further confirmed through cytotoxicity assays and molecular docking studies. Docking analysis revealed favorable binding interactions within the ACE2 active site, supporting the potential of compound 4 as a therapeutic agent. These findings provide a foundation for future in vivo studies and highlight the potential development of novel therapeutics targeting ACE2-related diseases, including COVID-19....
Herein, a novel series of 4-piperidinylphenyl-linked thiazoles was synthesized as VEGFR2 inhibitors with potential cytotoxic activity against renal cancer. Most of the target compounds inhibited VEGFR2 enzyme at sub-micromolar IC50 values. Compounds 7c (IC50 = 0.073 ± 0.002 μM), 9b (IC50 = 0.049 ± 0.002 μM), and 9c (IC50 = 0.093 ± 0.003 μM) were the most potent, showing VEGFR2 inhibition superior to that of sunitinib (IC50 = 0.118 ± 0.003 μM). Furthermore, compounds 7c, 9b, and 9c effectively inhibited the growth of A498 renal cancer cells, with compound 7c being the most potent showing a one-digit IC50 value of 7.866 ± 0.27 μM. In addition, compound 7c revealed a potentially improved safety profile against non-cancerous normal cells, relative to sunitinib. The treatment of A498 renal cancer cells with compound 7c led to an apparent cell cycle arrest and a significant induction of apoptosis. A docking study was also conducted and revealed a proper orientation of compound 7c into the active site of VEGFR2....
Background/Objectives: Antimicrobial resistance (AMR) presents a medical risk as well as a significant global socioeconomic challenge. Key contributors to AMR include the excessive use and incorrect application of antibiotics in humans and agriculture, nosocomial infections, and the absence of new classes of antibiotics. Methods: Novel dibrominated tricyclic flavonoids have been synthesized from the corresponding 3-dithiocarbamic flavanones and their antimicrobial and cytotoxicity properties have been investigated. Results: It has been found that these tricyclic flavonoids exhibit strong antimicrobial properties against clinically relevant pathogens such as Staphylococcus aureus, Acinetobacter baumannii, and Escherichia coli with MIC and MBC values against S. aureus ATCC 25923 as low as 0.12 μg/mL and 1.9 μg/mL, respectively. Conclusions: The synthetic tricyclic flavonoids exhibit strong antibacterial activity against selected WHO priority pathogens, including Staphylococcus aureus and Acinetobacter baumannii, surpassing the efficacy of both natural and synthetic flavonoids and several conventional antibiotics....
Spirocyclic compounds are experiencing a research surge due to their unique 3D structure, offering enhanced pharmacological, industrial, and material applications. They are increasingly used in medicinal chemistry to improve drug-like properties, such as solubility and target binding, and are also being utilized for advanced material applications, including electronics and photonics. In this communication, 3-(4-hydroxyphenyl)-1,3,6-trimethyl- 2H,3H,4H-spiro[furo[3,2-c]pyran-2,5-pyrimidine]-2,4,4,6(1H,3H)-tetraone was prepared via a two-stage transformation including a tandem Knoevenagel–Michael reaction and NBSinduced cyclization. At the first stage, a previously unknown ionic scaffold, morpholin-4- ium 5-((4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)(4-hydroxyphenyl)methyl)-1,3-dimethyl- 2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-olate was also isolated. Structures of the newly synthesized compounds were established by 1H and 13C NMR, IR spectroscopy, highresolution mass spectrometry, and elemental analysis....
Obtaining water-soluble palladium complexes capable of interacting with DNA is an important synthetic task in medicinal chemistry. The interaction of [Pd(phen)(OAc)2] (phen = 1,10-phenanthroline) with pivalic acid (tBuCOOH) and trifluoromethanesulfonic acid (HOTf) leads to the formation of the molecular complex [Pd(phen)(OOCtBu)2] (1) and the ionic complex [Pd(phen)(H2O)2]Otf2 (2), respectively. Complex 1 is highly soluble in water and stable in solution for 48 h. When complex 2 is boiled in water, it undergoes hydrolysis to form the binuclear hydroxo-bridged complex [Pd2(phen)2(μ-OH)2]Otf2 (3). According to X-ray diffraction data, the crystal lattices of 1–3 are stabilized by numerous intermolecular hydrogen bonds and π-π stacking interactions. The interaction of 1 and 2 with DNA in vitro (in 0.005 M NaCl solution) was studied using UV spectroscopy, low-gradient viscometry, and DNA melting analysis. It was shown that both compounds interact with DNA, and the binding is accompanied by the intercalation of the phenanthroline ligand at low concentrations in the DNA solution. An increase in their concentration leads to an alternative binding mode—palladium–DNA interaction causes a decrease in the DNA molecular coil size due to electrostatic interaction and/or palladium coordination to DNA bases. The difference between the binding of compounds 1 and 2 to DNA is that 2 can coordinate to N-bases, unlike complex 1. The antibacterial properties of the complexes have been studied in vitro against E. coli, P. aeruginosa, and S. aureus....
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