New Quinoxaline 1,4-Di-N-oxides: Anticancer and Hypoxia-Selective Therapeutic Agents. -A series of novel quinoxaline 1,4-di-N-oxides is prepared and evaluated for antitumor and hypoxia-selective cytotoxic activities. Compound (VIb) is the most promising substance acting both as an antitumor and as a hypoxia-selective agent. Compounds (IIIb) and (Xd) are the most toxic against liver carcinoma (Hepg2). -(ISMAIL*, M. M. F.; AMIN, K. M.; NOAMAN, E.; SOLIMAN, D. H.; AMMAR, Y. A.; Eur.
Facile synthesis
of molecular hybrids containing a 2,4-dinitrophenyl
moiety was achieved via nucleophilic aromatic substitution
of the fluoride anion of Sanger’s reagent (2,4-dinitrofluorobenzene)
with various N, S, and O nucleophiles, considered as bioactive moieties. Antimicrobial evaluation
of the new hybrids was carried out using amoxicillin and nystatin
as antibacterial and antifungal reference standards, respectively.
MIC test results identified the compounds 3, 4, and 7 as the most active hybrids against standard strains and
multidrug-resistant strains (MDR) of Staphylococcus
aureus, Escherichia coli, and Pseudomonas aurginosa. Most
of the hybrids displayed two times the antibacterial activity of AMOX
against MDR Pseudomonas aeruginosa, E. coli, and a standard strain of P. aeruginosa (ATCC 29853), while demonstrating a
weak antifungal profile against Candida albicans. Selectivity profiles of the promising compounds 3, 4, 6,
7, 8, and 11 on WI-38 human cells were characterized,
which indicated that compound 3 is the safest one (CC50 343.72 μM). The preferential anti-Gram-negative activity
of our compounds led us to do docking studies on DNA gyrase B. Docking
revealed that the potential antimicrobial compounds fit well into
the active site of DNA gyrase B. Furthermore, in silico absorption, distribution, metabolism, and excretion (ADME) predictions
revealed that most of the new compounds have high gastrointestinal
absorption and a good oral bioavailability with no BBB permeability.
FDA-approved antiviral agents represent an important class that has attracted attention in recent years to combat current and future threats of viral pandemics.
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