Current Issue : January-March Volume : 2026 Issue Number : 1 Articles : 5 Articles
The present study reports the synthesis of novel quinolone derivatives and their evaluation for antibacterial activities. Structure–activity relationship (SAR) studies have showed that the 1,4-dihydro-4-oxo-3-pyridine carboxylic acid pharmacophore is essential for antibacterial activity. However, the rise of multidrug-resistant (MDR) pathogens has significantly reduced the clinical efficacy of several existing fluoroquinolones, thereby necessary for the development of new derivatives with enhanced potency, improved selectivity and activity against resistant strains. Structural modifications at positions N-1, C-7 and C-8 of the quinolone nucleus are known to modulate drug–target interactions, increase lipophilicity and improve cellular penetration, leading to superior biological activity. In this present work, lomefloxacin was employed as a prototype molecule for the synthesis of novel derivatives. The modification for this drug mainly involves an acylation reaction with chloroacetyl-chloride, resulting in the formation of N-(Chloroacetyl lomefloxacin) takes place. The modification is mainly done at C4 Position of the piperazine ring with a linker. The chloroacetyl chloride is a linker for the reaction. N-(Chloroacetyl lomefloxacin) Further reacts with substituted phenols to form aryl ether derivatives (3a-f). Here chlorine atomof thechloroacetyl group is replaced by an aryl ether moiety, by forming an ether bond. The synthesized compounds were characterized by melting point determination; elemental analysis, FT-IR, ¹H NMR and mass spectrometry and all spectral data were reported. Additionally, QSAR parameters such as calculated Log P and drug-likeness were determined for the synthesized compounds. Antibacterial activity was evaluated against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) strains at four concentrations (0.25, 0.5, 0.75, and 1.0 mg/mL), using lomefloxacin as the standard drug for comparison. Among the series, compounds 3a and 3b exhibited significant antibacterial activity against both Staphylococcus aureus and Escherichia coli, demonstrating their potential as promising antibacterial agents....
Diabetes mellitus affects over 500 million people globally and is expected to rise significantly in the coming decades. Existing antidiabetic drugs, including α-glucosidase and α-amylase inhibitors, often exhibit side effects and limited efficacy, prompting the search for safer alternatives. Hydrazone derivatives have shown promising antidiabetic activity due to their structural diversity and enzyme-targeting potential. In this study, 10 novel hydrazone compounds were synthesized and evaluated for their inhibitory effects against α-amylase and α-glucosidase. Compounds 8 and 10 showed the highest dual inhibition: compound 8 with IC50 = 30.21 ± 0.16 μM (α-amylase) and 38.06 ± 0.80 μM (α-glucosidase); compound 10 with IC50 = 34.49 ± 0.37 and 40.44 ± 0.23 μM, respectively. Cytotoxicity on HEK293 cells via MTT assay revealed IC50 values of 61.04 μM (compound 7) and 69.25 μM (compound 9), while other compounds and acarbose were nontoxic up to 100 μM. In silico drug-likeness analysis showed that 80% of the compounds complied with Lipinski’s rules, with topological polar surface area (TPSA) values ranging between 63 and 112 Å2. Gastrointestinal absorption was high for 7 out of 10 compounds; none showed blood−brain barrier permeability. Molecular docking confirmed strong binding interactions of compounds 8 and 10 with both enzymes’ active sites. These findings highlight hydrazone scaffolds as potent and safe candidates for further antidiabetic drug development....
The main objective of the study was to choose the best salicylic acid-based monomers through in silico research to improve the antibacterial effects of dental prostheses, refine the synthesis process of such monomers, and examine their antibacterial and antifungal properties in vitro, forecast the long-term stability in an oral biological environment using molecular docking software and synthesizing new copolymers. Based on their strong antibacterial activity and low toxicity compared to other derivatives, the allyl ester of salicylic acid (AESA) and the allyl ester of acetylsalicylic acid (AEASA) were chosen as the study objects. Salicylic and acetylsalicylic acids were esterified with allyl alcohol and allyl bromide in a variety of solvents and temperatures to synthesize AESA and AEASA. The optimal conditions were identified with a yield of 78%. IR spectroscopy was used to confirm the chemical structure of synthesized molecules. In the presence of peroxybenzoyl, the regularities of the polymerization process between the obtained monomer and oligoethylene macromonomer (PEMM) were examined. To obtain new antibacterial oligomers containing a salicylic group and to study their physico-chemical properties, a technology for obtaining the copolymers of AESA with PEMM was developed, and their physical, mechanical, and antimicrobial properties were studied....
In the present study, we synthesized nine new derivatives of 2-(cyclohexylamino)thiazol- 4(5H)-one and evaluated their inhibitory activity against 11β-hydroxysteroid dehydrogenase type 1 and 2 (11β-HSD1 and 11β-HSD2), an enzyme responsible for the progression of metabolic disorders and cancers. All obtained derivatives showed inhibitory potential against 11β-HSD1, and four of them highly inhibited 11β-HSD1 activity with IC50 values in the low micromolar range. The most active compound, 3h with IC50 = 0.04 μM, became a more potent and selective inhibitor than carbenoxolone. In addition to inhibition of 11β-HSD1, we investigated the antitumor potential and effects on intracellular redox homeostasis of all newly synthesized compounds on five cancer cell lines, namely human colon cancer (Caco-2), human pancreatic cancer (PANC-1), human glioma (U-118 MG), human breast cancer (MDA-MB-231), and skin melanoma (SK-MEL-30) and on healthy fibroblasts derived from the skin of a male neonate (BJ). Among the derivatives, all tested compounds were found to cause a decrease in cell viability for the MDA-MB-231 and Caco-2 lines and for compounds 3b–3i for SK-MEL-30. The redox-modulating activity was assessed by measuring the levels of reactive oxygen species (ROS), reactive nitrogen species (RNS), and reduced glutathione (GSH) using the same panel of cancer lines and normal cells. This study showed an increase in ROS levels for SK-MEL-30, Caco-2, and MDA-MB-231 lines, while in the case of GSH levels, its reduction was observed in most experimental sets. The presented data suggest that the tested compounds are promising therapeutic agents with dual action because they offer the possibility of simultaneous regulation of metabolic disorders by inhibiting 11β-HSD1 and play a key role in anticancer therapy, which makes them prospective candidates for further clinical studies....
Sinomenine has long been known as an anti-inflammatory drug, while poor efficiency and large-dose treatment had limited its further application. Five novel sinomenine 1-Br- 4-cinnamic acid esters derivatives 2a–2e were designed and synthesized to improve its analgesic and anti-inflammatory activity. All synthesized sinomenine derivatives were structurally confirmed by NMR and ESI-MS. Molecular docking results showed that compounds 2a–2e had stable binding to the GBP5 protein. The compounds 2a–2e showed stable binding to the GBP5 protein by molecular docking Pre-preparing the druggability of compounds 2a–2e by ADEMT 3.0 showed that each derivative had similar druggability to sinomenine. The analgesic activity of compounds 2a–2e was preliminarily determined by hot plate and acetic acid writhing experiments, while anti-neuroinflammatory effects were evaluated by a xylene-induced mouse ear edema model. The results of the hot plate method showed that the synthesized sinomenine derivatives 2a–2e had some analgesic effects. The results of the acetic acid writhing test showed that the analgesic effects of 2a, 2c, 2e were better than that of sinomenine, and the other derivatives were equivalent to sinomenine. Compound 2b showed excellent anti-inflammatory properties in mouse ear edema....
Loading....