Total Synthesis of Altissimacoumarin D, a Small Molecule Sirtuin1 Activator

Silva, Anna C.; Benelkebir, Hanae; Lopes, Rosângela S. C.; Lopes, Claudio C.; Ganesan, A.

doi:10.21577/0103-5053.20180021

Cited by 2 publications

(7 citation statements)

References 17 publications

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“…This compound was prepared as previously described [17]. 1 H NMR (400 MHz, CDCl 3 ) δ 3.98 (s, 6H), 7.28 (s, 1H), 8.0 (s, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 56.6, 60.9, 109.0, 112.9, 134.…”

Section: 4-dihydroxy-35-dimethoxybenzaldehydementioning

confidence: 99%

“…However, no other studies have been performed since then, which was probably a consequence of the difficulty of obtaining such compounds, considering that 3 kg of the tree bark provides 6.5 to 22 mg of the coumarins [16]. In a previous study by our group, we were able to perform the first total synthesis of altissimacoumarin D (Figure 1), the most active compound isolated from A. altissima by Dao et al [17]. In this study, we aimed to improve the total synthesis of altissimacoumarin D by decreasing the number of steps and toxic reagents used, avoiding high temperatures (e.g., ethylene glycol reflux) and the use of anhydrous solvents.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of Altissimacoumarin D and Other Prenylated Coumarins and Their Ability to Reverse the Multidrug Resistance Phenotype in Candida albicans

Silva

Moraes

Carmo

et al. 2023

JoF

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Azoles are the main antifungal agents employed in clinical practice to treat invasive candidiasis. Nonetheless, their efficacy is limited by fungal resistance mechanisms, mainly the overexpression of efflux pumps. Consequently, candidiasis has a worrisome death rate of 75%. One potential strategy to overcome efflux-mediated resistance is to inhibit this process. Ailanthus altissima is a Chinese tree that produces several active substances, including altissimacoumarin D. Due to the low yield of its extraction and the need to search for new drugs to treat candidiasis, this study aimed to synthesize altissimacoumarin D and its analogues, as well as evaluating their ability to reverse the resistance phenotype of Candida albicans. Coumarin isofraxidin was prepared via total synthesis through a solvent-free Knoevenagel condensation as the key step. Isofraxidin and other commercially available coumarins were alkylated with prenyl or geranyl groups to yield the natural product altissimacoumarin D and seven analogues. The antifungal activity of the coumarins and their ability to reverse the fungal resistance phenotype were assessed using microbroth methodologies. Toxicity was evaluated using erythrocytes and an in silico prediction. All compounds improved the antifungal activity of fluconazole by inhibiting efflux pumps, and ACS47 and ACS50 were the most active. None of the coumarins were toxic to erythrocytes. In silico predictions indicate that ACS47 and ACS50 may be safe for human use. ACS47 and ACS50 are promising candidates when used as adjuvants in the antifungal therapy against C. albicans-resistant strains.

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Section: 4-dihydroxy-35-dimethoxybenzaldehydementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis of Altissimacoumarin D and Other Prenylated Coumarins and Their Ability to Reverse the Multidrug Resistance Phenotype in Candida albicans

Silva

Moraes

Carmo

et al. 2023

JoF

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“…Regarding the aforementioned synthesis methods, Silva and co-workers used a modified Knoevenagel reaction, with environmental benefits, and a more significant yield (94%) [103]. The biosynthetic origin of coumarins involves the shikimic acid pathway, which it seems to be an important way for the biosynthesis of the C6-C3 units (phenylpropane derivatives).…”

Section: Synthesis and Biosynthesismentioning

confidence: 99%

“…IF was extracted (yield 94%) by dichloromethane after acidification of the solution with hydrochloric acid (2 M). The synthesis steps have shown in Scheme 1 a [ 103 ].…”

Section: Isofraxidinmentioning

confidence: 99%

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Isofraxidin: Synthesis, Biosynthesis, Isolation, Pharmacokinetic and Pharmacological Properties

et al. 2020

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Isofraxidin (7-hydroxy-6, 8-dimethoxy coumarin) (IF) is a hydroxy coumarin with several biological and pharmacological activities. The plant kingdom is of the most prominent sources of IF, which, among them, Eleutherococcus and Fraxinus are the well-known genera in which IF could be isolated/extracted from their species. Considering the complex pathophysiological mechanisms behind some diseases (e.g., cancer, neurodegenerative diseases, and heart diseases), introducing IF as a potent multi-target agent, which possesses several herbal sources and the multiple methods for isolation/purification/synthesis, along with the unique pharmacokinetic profile and low levels of side effects, could be of great importance. Accordingly, a comprehensive review was done without time limitations until February 2020. IF extraction methods include microwave, mechanochemical, and ultrasound, along with other conventional methods in the presence of semi-polar solvents such as ethyl acetate (EtOAc). In addition to the isolation methods, related synthesis protocols of IF is also of great importance. From the synthesis point of view, benzaldehyde derivatives are widely used as precursors for IF synthesis. Along with the methods of isolation and biosynthesis, IF pharmacokinetic studies showed hopeful in vivo results of its rapid absorption after oral uses, leading to different pharmacological effects. In this regard, IF targets varieties of inflammatory mediators including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), tumor necrosis factor-α (TNF-α), and matrix metalloproteinases (MMPs). thereby indicating anticancer, cardioprotective, and neuroprotective effects. This is the first review on the synthesis, biosynthesis, isolation, and pharmacokinetic and pharmacological properties of IF in combating different diseases.

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Total Synthesis of Altissimacoumarin D, a Small Molecule Sirtuin1 Activator

Cited by 2 publications

References 17 publications

Synthesis of Altissimacoumarin D and Other Prenylated Coumarins and Their Ability to Reverse the Multidrug Resistance Phenotype in Candida albicans

Synthesis of Altissimacoumarin D and Other Prenylated Coumarins and Their Ability to Reverse the Multidrug Resistance Phenotype in Candida albicans

Isofraxidin: Synthesis, Biosynthesis, Isolation, Pharmacokinetic and Pharmacological Properties

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