Palmeira, Andreia; Vasconcelos, M. Helena; Paiva, Ana; Fernandes, Miguel X.; Pinto, Madalena; Sousa, Emilia published the artcile< Dual inhibitors of P-glycoprotein and tumor cell growth: (Re)discovering thioxanthones>, Category: tetrahydroisoquinoline, the main research area is thioxanthone preparation antitumor glycoprotein SAR.
For many pathologies, there is a crescent effort to design multiple ligands that interact with a wide variety of targets. 1-Aminated thioxanthone derivatives were synthesized and assayed for their in vitro dual activity as antitumor agents and P-glycoprotein (P-gp) inhibitors. The approach was based on mol. hybridization of a thioxanthone scaffold, present in known antitumor drugs, and an amine, described as an important pharmacophoric feature for P-gp inhibition. A rational approach using homol. modeling and docking was used, to select the mols. to be synthesized by conventional or microwave-assisted Ullmann C-N cross-coupling reaction. The obtained aminated thioxanthones were highly effective at inhibiting P-gp and/or causing growth inhibition in a chronic myelogenous leukemia cell line, K562. Six of the aminated thioxanthones had GI50 values in the K562 cell line below 10 μM and 1-{[2-(diethylamino)ethyl]amino}-4-propoxy-9H-thioxanthen-9-one (37) had a GI50 concentration (1.90 μM) 6-fold lower than doxorubicin (11.89 μM) in the K562Dox cell line. The best P-gp inhibitor found was 1-[2-(1H-benzimidazol-2-yl)ethanamine]-4-propoxy-9H-thioxanthen-9-one (45), which caused an accumulation rate of rhodamine-123 similar to that caused by verapamil in the K562Dox resistant cell line, and a decrease in ATP consumption by P-gp. At a concentration of 10 μM, compound 45 caused a decrease of 12.5-fold in the GI50 value of doxorubicin in the K562Dox cell line, being 2-fold more potent than verapamil. From the overall results, the aminated thioxanthones represent a new class of P-gp inhibitors with improved efficacy in sensitizing a resistant P-gp overexpressing cell line (K562Dox) to doxorubicin.
Biochemical Pharmacology published new progress about Antitumor agents. 115955-90-3 belongs to class tetrahydroisoquinoline, and the molecular formula is C9H12N2, Category: tetrahydroisoquinoline.
Referemce:
Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem