10.1016/S0957-4166(98)00087-1
The research focuses on the asymmetric Diels–Alder addition of cyclopentadiene to chiral 1,4-naphthoquinones, with the aim of achieving high levels of diastereomeric excess. The purpose of this study was to develop a method for the stereoselective formation of cyclopentannulated products, which can be further transformed into pyranonaphthoquinones, a class of compounds related to the pyranonaphthoquinone antibiotics. The researchers used various chiral auxiliaries, including (R)-pantolactone, (S)-N-methyl-2-hydroxysuccinimide, and trans-2-phenylcyclohexanol, which when combined with Lewis acid conditions, led to significant asymmetric induction. The conclusions drawn from the study were that the use of chiral auxiliaries at C-2 of 1,4-naphthoquinones enabled up to 96% stereoinduction in Diels–Alder cycloadditions with cyclopentadiene. The chiral auxiliaries could be removed from the fragmented products in acceptable yields, allowing for the formation of cyclopentannulated pyranonaphthoquinone ring systems, similar to those found in nature.
10.1016/j.bmc.2008.08.009
The study titled "Novel naphthoquinone and quinolinedione inhibitors of CDC25 phosphatase activity with antiproliferative properties" investigates the synthesis and biological evaluation of new naphthoquinone and quinolinedione derivatives designed to inhibit CDC25 phosphatase activity, which is implicated in cancer progression. The researchers introduced carboxylic or malonic acid groups to these derivatives to mimic the phosphate moieties of Cyclin-Dependent Kinase (CDK) complexes, aiming to enhance interactions with CDC25B. The most effective compounds exhibited inhibitory activity against CDC25B with IC50 values in the 10 μM range and showed cytotoxicity against HeLa cells. The study also explored the effects of these compounds on cell cycle progression, revealing that compound 2e had moderate effects on cell cycle distribution, consistent with CDC25 inhibitory effects. The research suggests that further chemical optimization of these derivatives could lead to potent CDC25 inhibitors with potential applications in cancer treatment.
10.1039/c2ob25229e
The research focuses on the exploration of the trifluoromenadione core as a template for designing antimalarial redox-active agents that interact with glutathione reductase. The study involves the synthesis, electrochemical analysis, enzyme kinetics, and antimalarial activities of a series of 1,4-naphthoquinone derivatives, specifically focusing on their reactivity under quasi-physiological conditions in NADPH-dependent glutathione reductase reactions. The experiments utilized various reactants, including menadione, its fluoro-analogues, and atovaquone derivatives, and employed techniques such as cyclic voltammetry, enzyme assays involving human and Plasmodium falciparum glutathione reductases, mass spectrometry, and in vitro parasite cultures for assessing antiparasitic and cytotoxic effects. The analyses encompassed the determination of IC50 values, redox potentials, enzyme inhibition properties, and the chemical stability of the synthesized compounds. The research aimed to develop multitarget-directed drugs by combining the trifluoromenadione core with the alkyl chain of the antimalarial drug atovaquone, revealing a mechanism for the CF3 group as a leaving group and demonstrating potent antimalarial activity against malarial parasites in culture.
10.1016/j.bmc.2010.11.001
The research focuses on the synthesis and antibacterial activity study of a novel class of cationic anthraquinone analogs. The purpose of the study was to investigate the effect of leaving groups and additives on the selectivity between the formation of 1-alkyl-1H- and 2-alkyl-2H-naphtho[2,3-d]triazole-4,9-diones, which are analogs of anthraquinone or naphthoquinone fused with 1,2,3-triazole. The researchers developed a novel class of antibacterial cationic anthraquinone analogs that exhibit different antibacterial profiles. Notably, one lead compound, 4e, showed high potency and selectivity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), while showing modest activity against Gram-negative bacteria. Other lead compounds, 4f and 4g, exhibited broad antibacterial activity against both MRSA and vancomycin-resistant Enterococcus faecalis (VRE). The chemicals used in the process included naphthoquinone, sodium azide, alkyl halides, and various leaving groups such as bromide, chloride, tosylate, mesylate, and trifluoroacetate. The synthesis involved a one-pot cycloaddition process and subsequent methylation to improve solubility and bioavailability, leading to the development of cationic compounds with significant antibacterial activity. The conclusions of the study suggest that these cationic compounds could pave the way for the development of new therapeutic agents, especially due to their unique antibacterial profiles and potential to avoid complications like Clostridium difficile infection (CDI).
10.1016/j.tetlet.2013.03.022
The research focuses on the synthesis of the naphthoquinone core of novel ansamycins, such as hygrocins A–B and divergolides C–D, which are biologically important macrolides derived from actinomycetes and exhibit antimicrobial and anti-cancer activities. The study aims to develop a facile and cost-effective synthetic route starting from the inexpensive 2-hydroxy-3-methylbenzoic acid, utilizing naphthalenic synthon for further elaboration of the ansabridge via C5–C6 bond formation. The researchers employed a commercially available sterically demanding organomagnesium reagent as a model ansa chain and successfully converted the resulting alcohol to the naphthoquinone fragment in one pot. The synthesis route is amenable to large-scale production and sets the stage for the total synthesis of these biologically important novel ansamycins.
T+,
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