36298-13-2

Upstream product

• 90-33-5 7-hydroxy-4-methyl-chromen-2-one 
• 6138-90-5 geranyl bromide 
• 106-24-1 Geraniol 
• 108-46-3 recorcinol 
• 6138-90-5 trans-geranyl bromide 
• 5389-87-7 1-chloro-3,7-dimethylocta-2,6-diene 

Relevant academic research and scientific papers

Investigation of the cytotoxicity of bioinspired coumarin analogues towards human breast cancer cells

Abstract: Coumarins possess a wide array of therapeutic capabilities, but often with unclear mechanism of action. We tested a small library of 18 coumarin derivatives against human invasive breast ductal carcinoma cells with the capacity of each compound to inhibit cell proliferation scored, and the most potent coumarin analogues selected for further studies. Interestingly, the presence of two prenyloxy groups (5,7-diprenyloxy-4-methyl-coumarin, 4g) or the presence of octyloxy substituent (coumarin 4d) was found to increase the potency of compounds in breast cancer cells, but not against healthy human fibroblasts. The activity of potent compounds on breast cancer cells cultured more similarly to the conditions of the tumour microenvironment was also investigated, and increased toxicity was observed. Results suggest that tested coumarin derivatives could potentially reduce the growth of tumour mass. Moreover, their use as (combination) therapy in cancer treatment might have the potential of causing limited side effects. Graphic abstract: [Figure not available: see fulltext.].

Design, synthesis, and biological evaluation of novel FXR agonists based on auraptene

Farnesoid X receptor (FXR) has been considered as an attractive target for metabolic disorder and liver injury, while many current FXR agonists suffer from undesirable side effects, such as pruritus. Therefore, it is urgent to develop new structure types different from current FXR agonists. In this study, a series of structural optimizations were introduced to displace the unstable coumarin and geraniol scaffolds of auraptene (AUR), a novel and safe FXR agonist. All of these efforts led to the identification of compound 14, a potent FXR agonist with nearly fourfold higher activity than AUR. Molecular modeling study suggested that compound 14 fitted well with binding pocket, and formed the key ionic bond with His291 and Arg328. In acetaminophen-induced acute liver injury model, compound 14 exerts better therapeutic effect than that of AUR, which highlighting its pharmacological potential in the treatment of drug-induced liver injury.

Inhibitory effects of coumarin derivatives on tyrosinase

In this study, a series of coumarin derivatives were synthesized and their inhibitory effects on the activity of mushroom tyrosinase were evaluated. As a result of measuring the inhibition of tyrosinase activity of these derivatives, the compounds 3e (1.05 μM), 3f (0.83 μM), 3h (0.85 μM), 3i (1.05 μM), and 3k (0.67 μM) of the geranyloxycoumarin derivatives were highly active at a concentration of 0.8%. The geranyloxycoumarin derivatives exhibited better activity than the hydroxycoumarin derivatives. Among the geranyloxycoumarin derivatives, compound 3k was two times more active than arbutin, a positive control, at a concentration of 0.4%. The above results suggest that gerany-loxycoumarin derivatives have great potential for application as functional cosmetic ingredients with tyrosinase-inhibiting activity.

Natural and semisynthetic oxyprenylated aromatic compounds as stimulators or inhibitors of melanogenesis

It has been very recently shown how naturally occurring oxyprenylated coumarins are effective modulators of melanogenesis. In this short communication we wish to generalize the potentialities as skin tanning or whitening agents of a wider panel of natural and semisynthetic aromatic compounds, including coumarins, cinnamic and benzoic acids, cinnamaldehydes, benzaldehyde, and anthraquinone derivatives. A total number of 43 compounds have been tested assaying their capacity to inhibit or stimulate melanin biosynthesis in cultured murine Melan A cells. The wider number of chemicals herein under investigation allowed to depict a detailed structure-activity relationship, as the following: (a) benzoic acid derivatives are slightly pigmenting agent, for which the effect is more pronounced in compounds with longer O-side chains; (b) independently from the type of substitution, cinnamic acids are able to increase melanin biosynthesis, while benzaldehydes are able to decrease it; (c) coumarins with a 3,3-dimethylallyl or shorter skeletons as substituents in position 7 are tanning agents, while coumarins with farnesyloxy groups are whitening ones; (d) double oxyprenylation in position 6 and 7 and 3,3-dimethylallyl or geranyl skeletons have slight depigmenting capacities, while farnesyl skeletons tend to marginally increase the tanning effect; (e) the presence of electron withdrawing groups (acetyl, COOH, and -Cl) and geranyl or farnesyl oxyprenylated chains respectively in positions 3 and 7 of the coumarin nucleus lead to a whitening effect, and finally (f) oxyprenylated anthraquinones have only a weak depigmenting capacity.

Combined molecular modeling and cholinesterase inhibition studies on some natural and semisynthetic O-alkylcoumarin derivatives

Coumarins of synthetic or natural origins are an important chemical class exerting diverse pharmacological activities. In the present study, 26 novel O-alkylcoumarin derivatives were synthesized and have been tested at 100 μM for their in vitro inhibitory potential against acetylcholinesterase (AChE) and butyrlcholinesterase (BChE) targets which are the key enzymes playing role in the pathogenesis of Alzheimer's disease. Among the tested coumarins, none of them could inhibit AChE, whereas 12 of them exerted a marked and selective inhibition against BChE as compared to the reference (galanthamine, IC50 = 46.58 ± 0.91 μM). In fact, 10 of the active coumarins showed higher inhibition (IC50 = 7.01 ± 0.28 μM – 43.31 ± 3.63 μM) than that of galanthamine. The most active ones were revealed to be 7-styryloxycoumarin (IC50 = 7.01 ± 0.28 μM) and 7-isopentenyloxy-4-methylcoumarin (IC50 = 8.18 ± 0.74 μM). In addition to the in vitro tests, MetaCore/MetaDrug binary QSAR models and docking simulations were applied to evaluate the active compounds by ligand-based and target-driven approaches. The predicted pharmacokinetic profiles of the compounds suggested that the compounds reveal lipophilic character and permeate blood brain barrier (BBB) and the ADME models predict higher human serum protein binding percentages (>50%) for the compounds. The calculated docking scores indicated that the coumarins showing remarkable BChE inhibition possessed favorable free binding energies in interacting with the ligand-binding domain of the target. Therefore, our results disclose that O-alkylcoumarins are promising selective inhibitors of cholinesterase enzymes, particularly BChE in our case, which definitely deserve further studies.

Anti-influenza activity of monoterpene-containing substituted coumarins

Compounds simultaneously carrying the monoterpene and coumarin moieties have been tested for cytotoxicity and inhibition of activity against influenza virus A/California/07/09 (H1N1)pdm09. The structure of substituents in the coumarin framework, as well as the structure and the absolute configuration of the monoterpenoid moiety, are shown to significantly influence the anti-influenza activity and cytotoxicity of the compounds under study. The compounds with a bicyclic pinane framework exhibit the highest selectivity indices (the ratios between the cytotoxicity and the active dose). The derivative of (?)-myrtenol 15c, which is characterized by promising activity, low cytotoxicity, and synthetic accessibility, has the greatest potential among this group of compounds. It exhibited the highest activity when added to the infected cell culture at early stages of viral reproduction.

Spasmolytic activity of aurapten analogs

Seven coumaric compounds analogous to aurapten were synthesized. Their spasmolytic activity against Ba2+, acetylcholine and histamine was evaluated to investigate their structure-activity relationship. The results of the bioassay demonstrated the important roles of the cis type of double bond at C-2' and the epoxide between C-6' and 7'.

Pharmacological activities of the prenylcoumarins, developed from folk usage as a medicine of Peucedanum japonicum Thunb.

In connection with the chemical structure of coumarin 1 (a mixture of acetylangeloylkhellactone and acetyltigloylkhellactone), a compound isolated from Peucedanum japonicum Thunb., we synthesized eight coumarin compounds (3-10) and performed pharmacological studies on these nine compounds, as well as on another coumarin, praeruptorin A (=Pd-Ia) (2), a compound isolated from Peucedanum praeruptorum Dunn. We studied the effects of compounds 1-5 on isolated smooth muscle and of compounds 1-10 on the cardiovascular system. These compounds showed dose-related antagonistic effects on histamin- and Ca2+-induced contractions in smooth muscle and the potencies were in the order 2 > 1 > seselin (3) > xanthyletin (4) = 2,2,10-trimethyl-2H,8H,benzo[1,2-b:3,4-b']dipyran-8-one (5). All the compounds except 7-geranyloxy-4-methylcoumarin (10) produced a dose-related increased in vertebral, carotid and femoral blood flow. Compounds 1, 5, and 4-methyl-7-(3-methyl-2-butenyloxy)coumarin (8) caused an increase in blood pressure, but 3 and 4 caused a slight decrease. Compounds 2, 3, 4, 5, and 8 increased heart rate. Jatamansinone (6) and jatamansinol (7) caused only slight changes in blood pressure. All the compounds except 10 increased heart rate. Compound 1 also increased blood flow in the cerebral cortex. Thus, compound 1 was confirmed to have an inhibitory effect on contraction in isolated smooth muscle and an action increasing arterial blood flow. Among the compounds tested in this study, 3, as well as 6 and 7 synthesized on the basis of 3, showed actions similar to those of Ca2+ blockers and some compounds had papaverine-like activities. These results suggest that the chemical moiety of compound 3 may be the basis for the pharmacological activities of Peucedanum japonicum Thunb.