- Discovery of Sustainable Drugs for Neglected Tropical Diseases: Cashew Nut Shell Liquid (CNSL)-Based Hybrids Target Mitochondrial Function and ATP Production in Trypanosoma brucei
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In the search for effective and sustainable drugs for human African trypanosomiasis (HAT), we developed hybrid compounds by merging the structural features of quinone 4 (2-phenoxynaphthalene-1,4-dione) with those of phenolic constituents from cashew nut s
- Cerone, Michela,Uliassi, Elisa,Prati, Federica,Ebiloma, Godwin U.,Lemgruber, Leandro,Bergamini, Christian,Watson, David G.,de A. M. Ferreira, Thais,Roth Cardoso, Gabriella Sim?es Heyn,Soares Romeiro, Luiz A.,de Koning, Harry P.,Bolognesi, Maria Laura
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Read Online
- Phenolic Lipids Derived from Cashew Nut Shell Liquid to Treat Metabolic Diseases
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Metabolic diseases are increasing at staggering rates globally. The peroxisome proliferator-activated receptors (PPARα/γ/δ) are fatty acid sensors that help mitigate imbalances between energy uptake and utilization. Herein, we report compounds derived from phenolic lipids present in cashew nut shell liquid (CNSL), an abundant waste byproduct, in an effort to create effective, accessible, and sustainable drugs. Derivatives of anacardic acid and cardanol were tested for PPAR activity in HEK293 cell co-transfection assays, primary hepatocytes, and 3T3-L1 adipocytes. In vivo studies using PPAR-expressing zebrafish embryos identified CNSL derivatives with varying tissue-specific activities. LDT409 (23) is an analogue of cardanol with partial agonist activity for PPARα and PPARγ. Pharmacokinetic profiling showed that 23 is orally bioavailable with a half-life of 4 h in mice. CNSL derivatives represent a sustainable source of selective PPAR modulators with balanced intermediate affinities (EC50 ~100 nM to 10 μM) that provide distinct and favorable gene activation profiles for the treatment of diabetes and obesity.
- Sahin, Cigdem,Magomedova, Lilia,Ferreira, Thais A. M.,Liu, Jiabao,Tiefenbach, Jens,Alves, Priscilla S.,Queiroz, Fellipe J. G.,Oliveira, Andressa S. De,Bhattacharyya, Mousumi,Grouleff, Julie,Nogueira, Patrícia C. N.,Silveira, Edilberto R.,Moreira, Daniel C.,Leite, José Roberto Souza De Almeida,Brand, Guilherme D.,Uehling, David,Poda, Gennady,Krause, Henry,Cummins, Carolyn L.,Romeiro, Luiz A. S.
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p. 1961 - 1978
(2022/02/14)
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- COMPOUNDS HAVING EXCITED STATE INTRAMOLECULAR PROTON TRANSFER (ESIPT) CHARACTER FOR USE IN TREATING AND/OR PREVENTING SUNBURN AND/OR PREVENTING U.V. DAMAGE
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This disclosure relates to use of cashew nut shell liquid (CNSL) phenolics in the manufacture of molecules having ESIPT character, wherein said molecules are UVA and/or UVB absorbers, and further wherein said molecules are formulated as protectants against UVA and/or UVB radiation. The disclosure extends to use of CNSL in the manufacture of compositions including molecules having ESIPT character for treating and/or preventing sunburn and/or preventing U.V. damage.
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Page/Page column 20-21
(2020/09/27)
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- Valorisation of Cashew Nut Shell Liquid Phenolics in the Synthesis of UV Absorbers
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With current concerns over the use of fossil resources for chemical synthesis of functional molecules and the effect of current UV absorbers in sunscreens have on the ecosystem, we describe a xylochemical synthesis of different classes of aromatic UV absorbers utilizing cashew nut shell liquid as a non-edible bio-renewable carbon source. Hydroxybenzophenones, xanthones, triazines, and flavones were synthesized starting from cardanol or anacardic acid. Several compounds exhibited favorable UVA and UVB absorption characteristics.
- Ngwira, Kennedy J.,Kühlborn, Jonas,Mgani, Quintino A.,de Koning, Charles B.,Opatz, Till
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p. 4778 - 4790
(2019/08/07)
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- Improved inhibition of the histone acetyltransferase PCAF by an anacardic acid derivative
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Several lines of evidence indicate that histone acetyltransferases (HATs) are novel drug targets for treatment of diseases like, for example, cancer and inflammation. The natural product anacardic acid is a starting point for development of small molecule inhibitors of the histone acetyltransferase (HAT) p300/CBP associated factor (PCAF). In order to optimize the inhibitory potency, a binding model for PCAF inhibition by anacardic acid was proposed and new anacardic acid derivatives were designed. Ten new derivatives were synthesized using a novel synthetic route. One compound showed a twofold improved inhibitory potency for the PCAF HAT activity and a twofold improved inhibition of histone acetylation in HEP G2 cells.
- Ghizzoni, Massimo,Boltjes, André,Graaf, Chris De,Haisma, Hidde J.,Dekker, Frank J.
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experimental part
p. 5826 - 5834
(2010/10/01)
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- Design, synthesis and biological evaluation of benzimidazole/benzothiazole and benzoxazole derivatives as cyclooxygenase inhibitors
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We have synthesised a series of 2-[[2-alkoxy-6-pentadecylphenyl)methyl]thio]-1H-benzimidazoles/benzothiazoles and benzoxazoles from anacardic acid and investigated their ability to inhibit human cyclooxygenase-2 enzyme (COX-2). The active compounds were s
- Paramashivappa,Phani Kumar,Subba Rao,Srinivasa Rao
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p. 657 - 660
(2007/10/03)
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- Synthesis of Anacardic Acids
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The anacardic acids 1-11, isolated from various plants, were synthesized by a new general method.Reaction of the methyl alkynoates 12-18 with 1-methoxy-1,4-cyclohexadiene at 200 deg C afforded directly the methyl 2-methoxybenzoates 19-25 with long chain substituents in 6-position in 74-85percent yield.The dienophiles 12-16 were prepared by pyrolysis of the corresponding acylphosphoranes 26-30, the dienophiles 17 and 18 by methoxycarbonylation of the corresponding alkynes 31 and 32 via the hydroxy esters 33 and 34.Demethylation of 19-23 with AlI3 gave the methyl salicylates 35-39 which could be hydrolized to the anacardic acids 1-4 and 7.Hydrolysis of 24 and 25 provided the hydroxy acids 40 and 41, which were converted by treatment with CBr4/PPh3 into the acids 42 and 43 bearing bromoalkyl side chains.These were transformed into 44-47 by reaction with 1-hexynyllithium and 1-octynyllithium.Stereoselective hydrogenation of 44-47 gave 48-51 with (Z)-alkene side chains.In a similar approach 42 was converted into 52 and then into 53, which gave upon treatment with 1-pentynylmagnesium bromide or 1-heptynylmagnesium bromide the acids 54 and 55 with alkadiyne side chains.Stereoselective hydrogenation provided 56 and 57 with (Z,Z)-alkadiene side chains.The 2-methoxy group in 48-51, 56, 57 was demethylated by treatment with AlI3 to give the anacardic acids 5, 6, 8-11. - Keywords: Anacardic acids; Benzoates, methyl 6-alkyl-2-methoxy-; 2-Alkynoates, methyl; Aluminium triiodide, demethylation by treatment with
- Zehnter, Reinhard,Gerlach, Hans
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p. 2209 - 2220
(2007/10/03)
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- Long-chain Phenols. Part 18. Conversion of Anacardic Acid into Urushiol
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(15:0)-Anacardic acid (6-pentadecylsalicylic acid), prepared by reduction of unsaturated anacardic acid from Anacardium occidentale, has been converted into anacardic alcohol (6-pentadecylsalicylic alcohol) and thence by oxidation at carbon into anacardaldehyde.Phenolic oxidation of anacardic alcohol led to 8-pentadecyl-1-oxaspiroocta-5,7-dien-4-one, itself readily convertible photochemically, but less so thermally, into anacardaldehyde.Reaction of thionyl chloride with anacardic acid led mainly to the anhydride, which by hydride reduction gave anacardaldehyde less satisfactorily.Dakin oxidation of anacardaldehyde furnished (15:0)-urushiol (3-pentadecylcatechol) identical chemically and from argentation t.l.c. with the hydrogenated natural product from Rhus vernicifera. (15:0)-Cardanol (3-pentadecylphenol) has been detected in hydrogenated urushiol.The composition of the unsaturated constituents of urushiol from Rhus vernicifera and Rhus toxicodendron and its mode of formation have been discussed.An improved synthesis of (15:0)-urushiol has been devised based on an organo-lithium route.Aromatic methyl ether and ester formation in this series is greatly facilitated by phase-transfer catalysis.
- Kiong, Lam Soot,Tyman, John H. P.
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p. 1942 - 1952
(2007/10/02)
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