2,4-Dihydroxybenzoic acid

Establishment of a UPLC-PDA/ESI-Q-TOF/MS-Based Approach for the Simultaneous Analysis of Multiple Phenolic Compounds in Amaranth (A. cruentus and A. tricolor).[Pubmed:33271996]

Molecules. 2020 Dec 1;25(23). pii: molecules25235674.

We used ultraperformance liquid chromatography coupled with a photodiode-array detector and electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-PDA/ESI-Q-TOF/MS) to rapidly and accurately quantify 17 phenolic compounds. Then, we applied this method to the seed and leaf extracts of two Amaranthus species to identify and quantify phenolic compounds other than the 17 compounds mentioned above. Compounds were eluted within 30 min on a C18 column using a mobile phase (water and acetonitrile) containing 0.1% formic acid, and the specific wavelength and ion information of the compounds obtained by PDA and ESI-Q-TOF/MS were confirmed. The proposed method showed good linearity (r(2) > 0.990). Limits of detection and quantification were less than 0.1 and 0.1 mug/mL, respectively. Intra- and interday precision were less than 2.4% and 1.8%, respectively. Analysis of amaranth seed and leaf extracts using the established method showed that the seeds contained high amounts of 2,4-Dihydroxybenzoic acid and kaempferol, and leaves contained diverse phenolic compounds. In addition, six tentatively new phenolic compounds were identified. Moreover, seeds potentially contained 2,3-dihydroxybenzaldehyde, a beneficial bioactive compound. Thus, our method was an efficient approach for the qualitative and quantitative analysis of phenolic compounds, and could be used to investigate phenolic compounds in plants.

Beta resorcylic acid lactones (RALs) from fungi: chemistry, biology, and biosynthesis.[Pubmed:33113097]

Arch Pharm Res. 2020 Nov;43(11):1093-1113.

beta-Resorcylic acid lactones (RALs) are one of the major polyketides produced by fungi, and some of them have a diverse array of biological activities. Most RALs feature a 14-membered macrocyclic ring fused to beta-resorcylic acid (2,4-Dihydroxybenzoic acid). In this review, more than 100 RAL-type of compounds are structurally classified into three groups; 14-membered RALs with 17R configuration, 14-membered RALs with 17S configuration, and benzopyranones/benzofuranones, and they are reviewed comprehensively in terms of chemistry, biological activities, and biosynthetic pathways.

Effects of Three Artificial Diets on Life History Parameters of the Ladybird Beetle Stethorus gilvifrons, a Predator of Tetranychid Mites.[Pubmed:32882791]

Insects. 2020 Sep 1;11(9). pii: insects11090579.

BACKGROUND: The ladybird beetle Stethorus gilvifrons (Mulsant) is an important natural enemy of tetranychid mites and functions as a biological control of these plant pests. The development, survival and reproduction of S. gilvifrons were studied when fed on three artificial diets. The components of the artificial diet that S. gilvifrons could be reared successfully on for one generation with no use of tetranychid mites were examined. METHODS: Artificial diets consisted of sucrose, honey, royal jelly, agar, yeast, date palm pollen supplemented in different diets with hen's egg yolk (AD1, as basic diet), Ephestia kuehniella Zeller eggs (AD2), or E. kuehniella eggs and 2,4-Dihydroxybenzoic acid (AD3). RESULTS: Adults and larvae of Stethorusgilvifrons fed on AD1 had a shorter immature development and preoviposition periods than those fed on AD2 and AD3. The total number of deposited eggs was significantly higher for the females fed on AD3 than on the other diets. The intrinsic rate of increase (r) of S. gilvifrons was highest on AD3, followed by AD2, and AD1. CONCLUSION: Stethorus gilvifrons performed best on AD3, indicating the potential of this artificial diet for the mass rearing of this important predatory ladybird beetle.

Camu-camu (Myrciaria dubia) seeds as a novel source of bioactive compounds with promising antimalarial and antischistosomicidal properties.[Pubmed:32846532]

Food Res Int. 2020 Oct;136:109334.

Parasitic diseases have attracted worldwide attention of their consequent impact on mortality and morbidity. Accordingly, several plants have been screened for antiparasitic activity aiming to create new alternatives for treatment. These diseases have been neglected and have not attracted worldwide attention (nowadays), the health concerns are focused in chronic diseases, but it is necessary to focus on parasitic diseases and look for prophylactic alternatives, such as plant extracts. Although camu-camu (Myrciaria dubia) seeds are a rich source of antioxidant antimutagenic, cytotoxic, anti-inflammatory, antimicrobial, antihypertensive and neuroprotective compounds, nothing is known about their antiparasitic effects. Thus, in the present study we aimed to evaluate five extracts of camu-camu seeds (100% water, 100% ethyl alcohol, 50% water + 50% ethyl alcohol, 25% water + 75% ethyl alcohol, and 75% water + 25% ethyl alcohol) in relation to their in vitro antimalarial, antischistosomicidal, leishmanicidal and anti-hemolytic effects. The extracts exhibited antischistosomicidal (ED50 values from 418.4 to >1000.0 microg/mL) and antimalarial activities (IC50 values from 24.2 to 240.8 microg/mL) for both W2 and 3D7 strains in all intra-erythrocytic stages. Correlation analysis showed that the toxic effects may mainly be attributed to methylvescalagin (r = -0.548 to -0.951, p < 0.05) and 2,4-Dihydroxybenzoic acid (r = -0.612 to -0.917, p < 0.05) contents. Moreover, the anti-hemolytic effect was associated to methylvescalagin (r = -0.597, p < 0.05). No toxic effects were observed for leishmaniasis and IMR90 normal cells. Herein, methylvescalagin was the bioactive compound of greatest interest once it presented simultaneous relation with antiparasitic and anti-hemolytic activities.

Structural variety of clofaziminium salts: effect of the counter-ion on clofaziminium conformation and crystal packing.[Pubmed:32830723]

Acta Crystallogr B Struct Sci Cryst Eng Mater. 2019 Aug 1;75(Pt 4):674-686.

Clofazimine is a water-insoluble antimycobacterial agent gaining attention as a treatment for multi-drug resistant and extensively drug-resistant tuberculosis. Novel salts of clofazimine are reported with fumaric, succinic, 2,4-dihydroxybenzoic and terephthalic acids and with saccharin. The salt structures were obtained by single-crystal X-ray diffraction. The salts with 2,4-Dihydroxybenzoic acid and with saccharin are solvated (methanol and acetonitrile, respectively). The reaction of clofazimine with terephthalic acid led to two salt cocrystals, one solvated and one non-solvated. These new clofaziminium salts are compared with the currently known ones in terms of crystal packing and clofazimine/ium conformation. Clofaziminium hydrogen succinate presents isostructurality with clofaziminium hydrogen malonate, an already described salt. In the structure of clofaziminium terephthalate terephthalic acid salt cocrystal, solvent evaporation leads to packing and hydrogen-bonding modifications. In all the new structures, the clofaziminium conformation is quite well conserved and steric hindrance is observed around the protonated site. Conformational optimization of clofaziminium reveals that this steric-hindrance energy penalty is compensated for by hydrogen-bond interactions with the salt counter-ions.

Screening, gene cloning, and characterization of orsellinic acid decarboxylase from Arthrobacter sp. K8 for regio-selective carboxylation of resorcinol derivatives.[Pubmed:32828832]

J Biotechnol. 2020 Nov 10;323:128-135.

Toward a sustainable synthesis of value-added chemicals, the method of CO2 utilization attracts great interest in chemical process engineering. Biotechnological CO2 fixation is a promising technology; however, efficient methods that can fix carbon dioxide are still limited. Instead, some parts of microbial decarboxylases allow the introduction of carboxy group into phenolic compounds using bicarbonate ion as a C1 building block. Here, we identified a unique decarboxylase from Arthrobacter sp. K8 that acts on resorcinol derivatives. A high-throughput colorimetric decarboxylase assay facilitated gene cloning of orsellinic acid decarboxylase from genomic DNA library of strain K8. Sequence analysis revealed that the orsellinic acid decarboxylase belonged to amidohydrolase 2 family, but shared low amino acid sequence identity with those of related decarboxylases. Enzymatic characterization unveiled that the decarboxylase introduces a carboxy group in a highly regio-selective manner. We applied the decarboxylase to enzymatic carboxylation of resorcinol derivatives. Using Escherichia coli expressing the decarboxylase gene as a whole cell biocatalyst, orsellinic acid, 2,4-Dihydroxybenzoic acid, and 4-methoxysalicylic acid were produced in the presence of saturated bicarbonate. These findings could provide new insights into the production of useful phenolic acids from resorcinol derivatives.

Fluorescence quantum yields of matrices used in ultraviolet matrix-assisted laser desorption/ionization.[Pubmed:32469439]

Rapid Commun Mass Spectrom. 2020 Sep 30;34(18):e8846.

RATIONALE: Ultraviolet matrix-assisted laser desorption/ionization (MALDI) is among the most popular soft ionization methods in mass spectrometry. Several theoretical models have been proposed to explain the primary ion generation in MALDI. These models require knowledge of various matrix molecular parameters for simulation. One such parameter is the fluorescence quantum yield. However, the fluorescence quantum yield reported in previous studies remains controversial. METHODS: In this study, we used a commercial and a homemade integrating sphere to measure the absorption and fluorescence quantum yields of several commonly used matrices, including 2,3-dihydroxybenzoic acid, 2,4-Dihydroxybenzoic acid (2,4-DHB), 2,5-dihydroxybenzoic acid (2,5-DHB), 2,6-dihydroxybenzoic acid, 3,4-dihydroxybenzoic acid, 3,5-dihydroxybenzoic acid, alpha-cyano-4-hydroxycinnamic acid, 2,4,6-trihydroxyacetophenone, and ferulic acid. RESULTS: The fluorescence quantum yields of these matrices were determined to be low (<0.08) at low laser fluences and decreased as the laser fluence increased. The fluorescence quantum yields at the typical laser fluence for MALDI are below 0.04 (2,4-DHB and 2,5-DHB) and 0.01 (the other matrices). Shot-to-shot fluctuations of fluorescence intensity and absorption are not directly related to the fluctuation of ions. Possible mechanisms for the decrease in the fluorescence quantum yield as the laser fluence increased were discussed. CONCLUSIONS: The fluorescence quantum yields of these commonly used matrices are much lower than those reported in previous studies. Although fluorescence quantum yield is an important parameter and it is crucial to obtain an accurate value for theoretical models in simulations, the use of fluorescence quantum yield alone is not a sufficient parameter to justify these models.

ADCK4 Deficiency Destabilizes the Coenzyme Q Complex, Which Is Rescued by 2,4-Dihydroxybenzoic Acid Treatment.[Pubmed:32381600]

J Am Soc Nephrol. 2020 Jun;31(6):1191-1211.

BACKGROUND: Mutations in ADCK4 (aarF domain containing kinase 4) generally manifest as steroid-resistant nephrotic syndrome and induce coenzyme Q10 (CoQ10) deficiency. However, the molecular mechanisms underlying steroid-resistant nephrotic syndrome resulting from ADCK4 mutations are not well understood, largely because the function of ADCK4 remains unknown. METHODS: To elucidate the ADCK4's function in podocytes, we generated a podocyte-specific, Adck4-knockout mouse model and a human podocyte cell line featuring knockout of ADCK4. These knockout mice and podocytes were then treated with 2,4-Dihydroxybenzoic acid (2,4-diHB), a CoQ10 precursor analogue, or with a vehicle only. We also performed proteomic mass spectrometry analysis to further elucidate ADCK4's function. RESULTS: Absence of Adck4 in mouse podocytes caused FSGS and albuminuria, recapitulating features of nephrotic syndrome caused by ADCK4 mutations. In vitro studies revealed that ADCK4-knockout podocytes had significantly reduced CoQ10 concentration, respiratory chain activity, and mitochondrial potential, and subsequently displayed an increase in the number of dysmorphic mitochondria. However, treatment of 3-month-old knockout mice or ADCK4-knockout cells with 2,4-diHB prevented the development of renal dysfunction and reversed mitochondrial dysfunction in podocytes. Moreover, ADCK4 interacted with mitochondrial proteins such as COQ5, as well as cytoplasmic proteins such as myosin and heat shock proteins. Thus, ADCK4 knockout decreased the COQ complex level, but overexpression of ADCK4 in ADCK4-knockout podocytes transfected with wild-type ADCK4 rescued the COQ5 level. CONCLUSIONS: Our study shows that ADCK4 is required for CoQ10 biosynthesis and mitochondrial function in podocytes, and suggests that ADCK4 in podocytes stabilizes proteins in complex Q in podocytes. Our study also suggests a potential treatment strategy for nephrotic syndrome resulting from ADCK4 mutations.