464894-91-5

Upstream product

• 1201808-13-0 2-(2,2-diphenylbenzo[d][1,3]dioxol-5-yl)-7-ethoxy-5-hydroxy-4H-chromen-4-one 
• 74-96-4 ethyl bromide 
• 491-70-3 2-(3,4-Dihydroxy-phenyl)-5,7-dihydroxy-chromen-4-on 

Relevant academic research and scientific papers

Selective synthesis of 7-O-substituted luteolin derivatives and their melanonenesis and proliferation inhibitory activity in B16 melanoma cells

In our previous study, the isolation of ugonin J, K, and L, which are luteolin derivatives, from the roots of Helminthostachys zeylanica and their identification as potent melanogenesis inhibitors, was described. The structure activity relationship (SAR) investigation in that study revealed that the catechol moiety in the B-ring of the flavone skeleton of ugonin K was important for its melanogenesis inhibitory activity, and the presence of the low polarity substituents at the C-7 position enhanced this activity. In order to further investigate the SAR of the C-7-substituent in the luteolin derivatives, different groups were selectively introduced at the C-7 position of luteolin after borax protection of the catechol hydroxyl group and the C-5 hydroxyl group. NMR and MS analysis of the borax protected derivatives revealed that the borax protects not only hydroxyl groups of catechol on the B ring but also the 5-hydroxyl group on the A ring. Eight luteolin derivatives were synthesized and evaluated for melanogenesis inhibitory effect in B16 melanoma cells. Two bulky groups and six alkoxyl groups were introduced at the C-7 position. The resulting luteolin derivatives showed improved melanogenesis and cell proliferation inhibitory activities. From among these derivatives, 7-O-hexylluteolin (7) showed the highest activity and inhibited the melanogenesis to 14% at 6.25 μM. The present study also revealed that the length of the carbon chain rather than the bulky substituent was more important for the melanogenesis inhibitory activity.

Synthesis of organic nitrates of luteolin as a novel class of potent aldose reductase inhibitors

Aldose reductase (AR) plays an important role in the design of drugs that prevent and treat diabetic complications. Aldose reductase inhibitors (ARIs) have received significant attentions as potent therapeutic drugs. Based on combination principles, three series of luteolin derivatives were synthesised and evaluated for their AR inhibitory activity and nitric oxide (NO)-releasing capacity in vitro. Eighteen compounds were found to be potent ARIs with IC 50 values ranging from (0.099 ± 0.008) μM to (2.833 ± 0.102) μM. O7-Nitrooxyethyl-O3′,O 4′-ethylidene luteolin (La1) showed the most potent AR inhibitory activity [IC50 = (0.099 ± 0.008) μM]. All organic nitrate derivatives released low concentrations of NO in the presence of l-cysteine. Structure-activity relationship studies suggested that introduction of an NO donor, protection of the catechol structure, and the ether chain of a 2-carbon spacer as a coupling chain on the luteolin scaffold all help increase the AR inhibitory activity of the resulting compound. This class of NO-donor luteolin derivatives as efficient ARIs offer a new concept for the development and design of new drug for preventive and therapeutic drugs for diabetic complications.

Discovery and synthesis of novel luteolin derivatives as DAT agonists

Luteolin, 5,7-dihydroxy-2-(3,4-dihydroxyphenyl)-4H-chromen-4-one, has been proposed and proved to be a novel dopamine transporter (DAT) activator. In order to develop this potential of luteolin, a series of novel luteolin derivatives were designed, synthesized, and evaluated for their DAT agonistic activities, utilizing constructed Chinese hamster ovary (CHO) cell lines stably expressing rat DAT. Biological screening results demonstrated that luteolin derivatives 1d, 1e, and 4c carry great DAT agonistic potency (EC50 = 0.046, 0.869, and 1.375 μM, respectively) compared with luteolin 8 (EC50 = 1.45 ± 0.29 μM). Luteolin derivative 1d, notably, exhibited a 32-fold-higher DAT agonistic potency than luteolin. These luteolin derivatives represent a novel DAT agonist class, from which lead compounds useful for exploration of additional novel DAT agonists could be drawn.