Synthesis and Biological Evaluation of new 1,2,4-triazinones functionalized with mono-substituted pyrazole heterocycles

A new series of functionalized 1,2,4-triazinones (11a-g) were synthesized via 1,3-dipolar cycloaddition reactions of L-α-amino esters (1a-g) with N-(5-methyl-1H-pyrazol-3-yl) nitrile amine, generated in situ from the reaction of N-(5-methyl-1H-pyrazol-3-yl)-2-oxopropanehydrazonyl chloride (9) and triethyl amine. The structures of the newly synthesized compounds were confirmed by spectroscopic methods (HRMS, 1H-NMR, 13C-NMR and 2D-NMR). Furthermore, their antibacterial, antioxidant and antitumor activity were evaluated. The results clearly showed that compounds 11a,11d and 11e acted as highly active antioxidants; while on the other hand, all synthesized compounds exhibited a weak antitumor and antibacterial activity.

A new efficient route to 7-aryl-6-fluoro-8-nitroquinolones as potent antibacterial agents

A series of 7-aryl-6-fluoro-8-nitroquinolones (6a-e) were synthesized through a novel, simple and clean synthetic procedure, through a Suzuki-Miyaura reaction. The target compounds were evaluated in vitro for their antimicrobial properties against bacterial and fungal strains. All of them showed antibacterial activity higher than the activity of ciprofloxacin, both towards Gram positive Bacillus subtilis and Staphylococcus aureus, and Gram negative Haemophilus influenzae strains. Compound 6d, containing the trisubstituted 7-aryl moiety, emerged as the most active quinolone derivative with MIC values ranging from 0.00007 µg/mL to 0.015 µg/mL

Synthesis and biological evaluation of tetracyclic thienopyridones as antibacterial and antitumor agents

A facile synthesis of model 4-oxopyrido[3',2':4,5]thieno[3,2-b]indole-3-carboxylic acids 9a-e was achieved via Stille arylation of 2-chloro-3-nitro-4-oxothieno[2,3-b]pyridine-5-carboxylate and a subsequent microwave-assisted phosphite-mediated Cadogan reaction. The new compounds were tested for their in vitro antimicrobial and antiproliferative activity. Compounds 9a-c and 9e exhibited very high potency against Gram positive Bacillus subtilis and Bacillus megaterium at concentrations 0.000015-0.007 μg/mL. They also displayed excellent activity towards other Gram positive bacilli and staphylococci and Gram negative Haemophilus influenzae, being in most cases superior or equal to commercial fluoroquinolones. Both 9a and 9c were inhibitors of the DNA gyrase activity. As concerns antitumor properties, compounds 9b-e showed growth inhibition of MCF-7 breast tumor and A549 non-small cell lung cancer cells with IC(50) 1.6-2.8 μM and 2.6-6.9 μM, respectively, coupled with absence of cytotoxicity towards normal cells. These compounds are promising as dual acting chemotherapeutics