Current Organic Synthesis - Current Issue

In this study, novel 1-(3-cyano-4,6-dimethyl-2-oxopyridin-1(2H)-yl)-3-phenylthiourea 2, 3-phenylthiazolidin-4-one 3, and arylidene-4-thiazolidinone derivatives 5a-k were synthesized in excellent yields. The produced compounds underwent assessment for their antimicrobial properties. Efficient and easy procedures for synthesizing arylidene-4-thiazolidinones 5a-k were delineated.

3-phenylthiazolidin-4-one 3 was achieved by reacting 1-(3-cyano-4,6-dimethyl-2-oxopyridin-1(2H)-yl)-3-phenylthiourea 2 with ethyl 2-bromoacetate in EtOH, employing anhydrous sodium acetate at reflux temperature. Furthermore, a sequence of arylidene-4-thiazolidinone derivatives 5a-k was synthesized by condensing 4-thiazolidinone 3 with different aromatic and heterocyclic aldehydes in a refluxing EtOH-containing piperidine. The binding mechanism of the thiazolidine derivatives to the dihydrofolate reductase (DHFR) and rhomboid protease proteins was determined by docking studies.

Compounds 2, 5c, 5d, 5g, and 5i exhibited germicidal effects against both Gram-negative and Gram-positive bacteria. Furthermore, these compounds exhibited antifungal properties. The MIC ranged from 250 to below 500 μg/mL. The docking study revealed a strong correlation between the docking solutions and the experimental observations.

The structure of new compounds was identified by analytical and spectroscopic data. Certain thiazolidines showed exceptional antibacterial and antifungal properties. These interactions require more investigations that are comprehensive.

Ribavirin is a 1,2,4-triazole nucleoside that has been used to treat hepatitis C virus infections. Previous studies have revealed a number of biological actions of 1,2,4-triazole and its Schiff bases, including herbicidal, fungicidal, anticancer, and antiviral activity. With readily available laboratory reagents, tartaric acid, and mercaptotriazolethanediol derivative, the authors aimed to synthesize and characterize some novel Schiff bases of the 1,2,4-triazole skeleton. Schiff bases are adaptable substances with a wide range of uses in biology and chemistry.

For obtaining Schiff bases of 1,2,4-triazole derivatives, the strategy involved synthesizing bis-mercapto-1,2,4- or/and 4-amino-5-(benzylthio)1,2,4-triazole and then reacting it with aromatic aldehydes, such as furfural, 4-amino N, N-dimethylbenzaldehyde, 4-cyanobenzaldehyde, 2,4-dichlorobenzaldehyde, and 4-hydroxybenzaldehyde in MeOH/HCl. The prepared structures were confirmed using IR, ¹H/¹³C NMR, and elemental analysis. The antimicrobial activity of the synthesized compounds was investigated against Gram +ve and Gram -ve bacteria, fungi, and yeast. Moreover, antitumor activity was tested for some compounds against one tumor cell line (MCF-7 cell line).

Schiff bases of some double-headed acyclic nucleosides of 1,2,4-triazole were synthesized with high yields in the range 52%-87%. Compounds 6, 7, 11, and 16 exhibited high antimicrobial activity. Compound 12 was considered the most active one, and it can potentially act as an antimicrobial agent compared with the standard references, Gentamycin and fluconazole. Finally, compounds 8 and 12 exhibited high antitumor activity. Compound 8 showed antitumor activity more than the reference drug cisplatin.

The structure of the synthesized Schiff bases of double-headed acyclic nucleosides of 1,2,4-triazole was established using elemental analysis, IR, MS, and ¹H/¹³C NMR spectroscopy. The activity of Schiff bases was significantly influenced by the substituent groups of the aromatic ring, particularly electron-donating and electron-withdrawing groups.

The authors recommend further experimental assessments of compounds 8 and 12 as antimicrobial and antitumor agents, considering their promising biological results.

8-Hydroxyquinoline derivatives are compounds isolated from plants that possess a wide range of pharmacological activities. In our previous work, a series of novel 8-hydroxyquinoline derivatives was synthesized. Among them, the compound 5c, 7-((4-(o-tolyl) piperazine-1-yl) methyl)-5-nitroquinolin-8-ol, demonstrated broad-spectrum antifungal activity against five plant pathogenic fungi with EC50 values ranging from 4.69 to 12.61 μg/mL.

This investigation principally focused on determining the potential mechanisms of compound 5c using Botrytis cinerea (B. cinerea) as a model.

The electron microscope observations revealed that after being treated with compound 5c at 5 μg/mL, the mycelia became obviously curved, collapsed, and its integrity of the cell membrane was eventually destroyed.

The compound 5c influenced the production of reactive oxygen species, loss of mitochondrial membrane potential, and nuclear morphology. In addition, compound 5c inhibited the enzyme activities related to mitochondrial function.

These findings will deepen our insights into the mechanisms of action of 8-hydroxyquinoline against B. cinerea and open new directions for the future development of effective antifungal agents to control phytopathogenic fungi.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline, with current treatments focused on inhibiting acetylcholinesterase (AChE) to sustain acetylcholine levels in brain.

In this work, three new calixarene derivatives 3, 5, and 7 were synthesized and evaluated against AChE in vitro and in silico.

Firstly, target compounds 3, 5, and 7 were synthesized from calix[4]arene (1), and after characterization, they were evaluated in vitro against AChE. The most potent compound, as determined by in vitro evaluation, underwent additional in silico studies, including a docking study, pharmacokinetics analysis, and density functional theory (DFT) analysis.

The most potent compound was the pyridin-2-yl-chalcone derivative 7, which interacted well with the active site of AChE. This compound also has an acceptable energy gap between HOMO and LUMO orbitals as a drug candidate. The pharmacokinetics and toxicity profiles of new calixarene derivatives 3, 5, and 7 were satisfactory.

The results of this study demonstrate that the newly synthesized calixarene derivatives, particularly compound 7, exhibit promising activity against acetylcholinesterase (AChE), both in vitro and through in silico analysis.

Our in vitro and in silico results suggest that the calixarene derivatives are promising candidates for targeting AChE.

Quinoline-based α-aminoamides are promising scaffolds in drug discovery due to their enhanced pharmaceutical properties and biological relevance. Developing efficient and environmentally friendly synthetic methods remain a key goal in pharmaceutical chemistry.

In this study, we developed a green synthetic approach using a Ugi three-component reaction (Ugi-3CR). The reaction involves 2-chloroquinoline-3-carbaldehyde, various aldehydes, and isocyanides in the presence of sodium lauryl sulfate (SLS) as a surfactant in water.

The optimized reaction conditions afforded the desired α-aminoamide products in moderate to good yields (59-79%), depending on the substrate used. The reaction worked well with a broad range of starting materials, showing its versatility and efficiency. The use of SLS in water not only promotes reaction efficiency but also aligns with green chemistry principles.

This work highlights how multicomponent reactions like the Ugi-3CR can simplify the synthesis of structurally diverse, biologically relevant molecules. The use of water and SLS also aligns with green chemistry goals, making the process both practical and environmentally conscious.

Our study presents a practical, green, and versatile strategy for the synthesis of quinoline-based α-aminoamides via Ugi-3CR, supporting their continued development in medicinal chemistry.