10.1016/j.bmc.2020.115798
The study focuses on the synthesis and evaluation of nitrogen-containing naringenin derivatives for their potential to reverse multidrug resistance (MDR) in cancer. The researchers aimed to develop small molecules that could inhibit drug efflux by ABC transporter proteins, particularly P-glycoprotein (P-gp/ABCB1), which is associated with MDR. A series of naringenin derivatives were synthesized through chemical modifications, including O-methylation and the introduction of nitrogen atoms and aromatic moieties at specific positions on the naringenin scaffold. These derivatives were tested for their cytotoxicity and ability to modulate P-gp in human ABCB1-transfected mouse T-lymphoma cells. The most promising compounds were further assessed for their synergistic effects when combined with the anticancer drug doxorubicin. The study also employed in silico approaches to understand the structural basis of the observed MDR-reversal activity. The chemicals used served as potential MDR reversers, helping to combat the resistance of cancer cells to chemotherapeutic drugs, and provided insights into the structural requirements for effective P-gp modulation.
10.1016/j.bmc.2014.04.016
The research focuses on the design and discovery of flavonoid-based HIV-1 integrase inhibitors that target both the active site of the enzyme and its interaction with LEDGF/p75. The purpose of this study is to develop novel inhibitors that can combat HIV-1 by inhibiting the viral replication process, specifically the integration of viral DNA into the host genome, which is catalyzed by HIV integrase (IN). The researchers synthesized a series of flavonoid derivatives with the aim of improving the inhibitory activity against IN and disrupting the IN-LEDGF/p75 interaction, which is crucial for viral integration. The study concluded that certain flavonoids, particularly those containing a catechol or β-ketoenol structure, showed potent inhibitory activity against both the catalytic function of IN and the IN-LEDGF/p75 interaction. Notably, the introduction of a hydrophilic morpholine group at the phenolic hydroxyl position resulted in sub- to low-micromolar IN-LEDGF/p75 inhibitory activity. The chemicals used in this process included various flavonoid derivatives, such as quercetin, baicalein, genistein, luteolin, chrysin, apigenin, and naringenin, along with synthetic reagents like acetic anhydride, benzyl bromide, potassium carbonate, and palladium catalysts for the synthesis and modification of these flavonoids.
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