10.1002/cmdc.201200154
The research focuses on the development of potent and highly selective inhibitors of the breast cancer resistance protein (ABCG2), a key factor in multidrug resistance in cancer cells. The study reports a one-step synthesis method for 6-halogenochromones linked to a tryptamine unit, which were evaluated for their inhibitory activity against ABCG2. The synthesis involved coupling 6-substituted-4-oxo-4H-chromene-2-carboxylic acid with tryptamine using bis(2-oxo-3-oxazolidinyl)phosphonic chloride (BOP-Cl) as the coupling agent. The synthesized compounds were screened for their effects on the inhibition of mitoxantrone efflux in ABCG2-transfected HEK293 cells, using flow cytometry. The most active compounds were further tested for selectivity against P-gp/ABCB1 and MRP1/ABCC1 transporters and evaluated for their cytotoxicity and ability to chemosensitize cancer cells to anticancer drugs like mitoxantrone and SN-38. The experiments included assays for drug transport, cytotoxicity, and sensitization to anticancer drugs, with analyses performed using flow cytometry and MTT colorimetric assays.
10.1021/jm060213k
The research focuses on the synthesis and evaluation of dopamine receptor antagonists based on the benzindoloazecine structure. The study aimed to modulate the affinities for dopamine D1-D5 receptors by homologizing a lead compound, LE 300. Two homologue antagonists were synthesized, and their affinities and inhibitory activities at D1-D5 receptors were measured using radioligand binding experiments and a functional Ca2+ assay. The phenylpropyl homologue 3 showed superior selectivity and affinity for the D5 subtype with a Ki of 0.6 nM, while the indolylpropyl homologue 2 exhibited decreased affinity for all subtypes. The experiments involved the synthesis of compounds 2 and 3 through a series of chemical reactions, including the use of tryptamine, lactone 15, and various reagents such as PCl5, POCl3, and NaBH4. The synthesized compounds were then tested for their binding affinities and inhibitory activities, with the results indicating significant differences in receptor affinities between the two homologues. The analyses used included radioligand binding studies and a calcium fluorescence assay to determine the inhibitory activity of the compounds at the dopamine receptors.
10.1021/jo00149a009
The research focuses on the synthesis and photooxidation of condensation products of tryptamine and catechol derivatives, aiming to approach the synthesis of a probable precursor of the Gelsemium alkaloid koumine. Key chemicals involved include tryptamine, 3,4-dihydroxyphenylpyruvic acid, isopropyl chloroformate, and lithium aluminum hydride. The study successfully synthesized compounds such as 1,3,5,6,14,21-hexahydro-17,18-dihydroxybenz-[g]indolo[2,3-a]quinolizine (2) and 3-ethoxy-3,4-seco-N-methyl-1,3,5,6,14,21-hexahydro-17,18-dihydroxybenz-[g]indolo[2,3-a]quinolizine (5), and achieved the cleavage of their catechol rings through photosensitized oxidation to obtain muconic acid derivatives 7 and 8. These compounds and their transformations played crucial roles in exploring the potential synthesis pathway of koumine.
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