Antibacterial activity of monoacetylated alkyl gallates against Xanthomonas citri subsp citri

Asiatic citrus canker (ACC) is an incurable disease of citrus plants caused by the Gram-negative bacterium Xanthomonas citri subsp. citri (X. citri). It affects all the commercially important citrus varieties in the major orange producing areas around the world. Control of the pathogen requires recurrent sprays of copper formulations that accumulate in soil and water reservoirs. Here, we describe the improvement of the alkyl gallates, which are potent anti-X. citri compounds, intended to be used as alternatives to copper in the control of ACC. Acetylation of alkyl gallates increased their lipophilicity, which resulted in potentiation of the antibacterial activity. X. citri exposed to the acetylated compounds exhibited increased cell length that is consistent with the disruption of the cell division apparatus. Finally, we show that inhibition of cell division is an indirect effect that seemed to be caused by membrane permeabilization, which is apparently the primary target of the acetylated alkyl gallates

Design of Antibacterial Agents:Alkyl Dihydroxybenzoates against Xanthomonas citri subsp. citri

Xanthomonas citri subsp. citri (Xcc) causes citrus canker, affecting sweet orange-producing areas around the world. The current chemical treatment available for this disease is based on cupric compounds. For this reason, the objective of this study was to design antibacterial agents. In order to do this, we analyzed the anti-Xcc activity of 36 alkyl dihydroxybenzoates and we found 14 active compounds. Among them, three esters with the lowest minimum inhibitory concentration values were selected; compounds 4 (52 μM), 16 (80 μM) and 28 (88 μM). Our study demonstrated that alkyl dihydroxybenzoates cause a delay in the exponential phase. The permeability capacity of alkyl dihydroxybenzoates in a quarter of MIC was compared to nisin (positive control). Compound 28 was the most effective (93.8), compared to compound 16 (41.3) and compound 4 (13.9) by percentage values. Finally, all three compounds showed inhibition of FtsZ GTPase activity, and promoted changes in protofilaments, leading to depolymerization, which prevents bacterial cell division. In conclusion, heptyl dihydroxybenzoates (compounds 4, 16 and 28) are promising anti-Xcc agents which may serve as an alternative for the control of citrus canker

Biological Membranes as Targets for Natural and Synthetic Compounds

Biological membranes are responsible for all types of regulation and compound transfer, as well as information flow between and within eukaryotic and prokaryotic cells [...

Use of glycerol, waste glycerol from biodiesel production and other protic solvents in bioactive α,β-unsaturated ketones synthesis

Glycerol is the main co-product from biodiesel production and has been recognized as a sustainable solvent. Herein, we used glycerol and waste glycerol in synthesis of two bioactive α,β-unsaturated ketones (E,E)-1,5-diphenylpenta-2,4-dien-1-one (1) and (E,E)-2,6-dibenzylidenecyclohexanone (2), using aldol mono- and di-condensation reactions, respectively. Crude yield values were calculated from product mass after precipitation and drying. Purity was measured by High Performance Liquid Chromatography with Photodiode Array (HPLC-PAD) using analytical curves and reference compounds. Glycerol and waste glycerol were able to furnish 1 and 2 in higher crude yields and HPLC-PAD purities values than other protic solvents (ethanol, methanol, PEG-400 and water). In order to investigate reasons of glycerol efficiency when compared to water efficiency, we performed computational calculations using Density Functional Theory (DFT). Theoretical predictions confirmed the E1cB mechanism, as well as favourable energy barrier using glycerol in comparison to water, corroborating their sustainable properties. In addition, waste glycerol from corn and sunflower oil transesterifications were used in the synthesis of 1 and 2 for four recycles, displaying good crude yields and HPLC-purities.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)São Paulo State University (Unesp) Institute of Biosciences Humanities and Exact Sciences (Ibilce), São José do Rio Preto, São PauloSão Paulo State University (Unesp) Institute of Biosciences Humanities and Exact Sciences (Ibilce), São José do Rio Preto, São PauloFAPESP: 2014/18330-0FAPESP: 2018/15083-2CNPq: 306251/2016-7CNPq: 309957/2019-2CNPq: 429322/2018-6CNPq: 471129/2013-

Human ABCB1 confers cells resistance to cytotoxic guanidine alkaloids from Pterogyne nitens

Multidrug resistance (MDR) caused by human ABCB1 (P-glycoprotein/MDR1) is one of the major obstacles in chemotherapy. To understand the mechanism of MDR by ABCB1 and circumvent the MDR, in the present study, we established human ABCB1-expressing cells (Flp-In-293/ABCB1 cells) and examined the cytotoxic effects of four guanidine alkaloids from Pterogyne nitens (galegine, nitensidine A, pterogynidine and pterogynine) using Flp-In-293/Mock and Flp-In-293/ABCB1 cells. The activity of ABCB1 in Flp-In-293/ABCB1 cells were confirmed by typical substrates for ABCB1 (taxol and vinblastine) in MTT assay. Flp-In-293/ABCB1 cells were also resistant to the four guanidine alkaloids as well as taxol and vinblastine compared to Flp-In-293/Mock cells although the four guanidine alkaloids exhibited cytotoxicity against the two Flp-In-293 cells. Furthermore, the four guanidine alkaloids were also found to stimulate the ATPase activity of ABCB1 in ATPase assays. These results suggest that ABCB1 can confer the resistance to the cytotoxic guanidine alkaloids by transporting them.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Hydroxychalcones as Herbicides

Efforts to develop weed management alternatives are urgently required due to various challenges, such as declining crop yields, rising production costs, and the growing prevalence of herbicide-resistant weed species. Chalcones occur in nature and have phytotoxic potential and concise synthesis; additionally, they are multifunctional, with diverse biomolecular targets and a broad spectrum of biological activities. This study sought to assess the herbicidal potential of 3′-hydroxychalcones against weed species under laboratory conditions. Their effects were investigated using germination bioassays, early growth measurements, and the seedling vigor index, all prepared with a concentration of 1 × 10−3 mol L−1 3′-hydroxychalcones. 3′-Hydroxy-4-pyridyl-chalcone caused the greatest inhibition (81%) of the seedling length in Urochloa decumbens. Other 3′-hydroxychalcones also caused large initial growth reductions, such as 3′-hydroxy-4-pyridyl-chalcone (75%) and 3′-hydroxy-4-nitrochalcone (68%) in Digitaria insularis and 3′-hydroxy-4-bromochalcone (73%) in Raphanus raphanistrum. The greatest reduction in the seedling vigor index was 81% in D. insularis treated with the 3′-hydroxy-4-bromochalcone. The same 3′-hydroxychalcone caused an 80% reduction in Amaranthus viridis. In conclusion, 3′-hydroxychalcones exhibit herbicidal activity, suggesting they could serve as a solution for future weed management strategies.Department of Biological Sciences São Paulo State University “Júlio de Mesquita Filho”, SPDepartment of Agricultural Biology Colorado State UniversityInstitute of Biosciences Humanities and Exact Sciences São Paulo State University “Júlio de Mesquita Filho”, São José do Rio Preto, SPDepartment of Biological Sciences São Paulo State University “Júlio de Mesquita Filho”, SPInstitute of Biosciences Humanities and Exact Sciences São Paulo State University “Júlio de Mesquita Filho”, São José do Rio Preto, S

Nitensidine A, a guanidine alkaloid from Pterogyne nitens, induces osteoclastic cell death

Nitensidine A is a guanidine alkaloid isolated from Pterogyne nitens, a common plant in South America. To gain insight into the biological activity of P. nitens-produced compounds, we examined herein their biological effects on osteoclasts, multinucleated giant cells that regulate bone metabolism by resorbing bone. Among four guanidine alkaloids (i.e., galegine, nitensidine A, pterogynidine, and pterogynine), nitensidine A and pterogynine exhibited anti-osteoclastic effects at 10 μM by reducing the number of osteoclasts on the culture plate whereas galegine and pterogynidine did not. The anti-osteoclastic activities of nitensidine A and pterogynine were exerted in a concentration-dependent manner, whereas nitensidine A exhibited an approximate threefold stronger effect than pterogynine (IC50 values: nitensidine A, 0.93 ± 0.024 μM; pterogynine, 2.7 ± 0.40 μM). In the present study, the anti-osteoclastic effects of two synthetic nitensidine A derivatives (nitensidine AT and AU) were also examined to gain insight into the structural features of nitensidine A that exert an anti-osteoclastic effect. The anti-osteoclastic effect of nitensidine A was greatly reduced by substituting the imino nitrogen atom in nitensidine A with sulfur or oxygen. According to the differences in chemical structures and anti-osteoclastic effects of the four guanidine alkaloids and the two synthetic nitensidine A derivatives, it is suggested that the number, binding site, and polymerization degree of isoprenyl moiety in the guanidine alkaloids and the imino nitrogen atom cooperatively contribute to their anti-osteoclastic effects. © 2013 Springer Science+Business Media Dordrecht

Inhibitory Effect of Gallic Acid and Its Esters on 2,2 '-Azobis(2-amidinopropane)hydrochloride (AAPH)-Induced Hemolysis and Depletion of Intracellular Glutathione in Erythrocytes

The protective effect of gallic acid and its esters, methyl, propyl, and lauryl gallate, against 2,2'-azobis(2-amidinopropane)hydrochloride (AAPH)-induced hemolysis and depletion of intracellular glutathione (GSH) in erythrocytes was studied. The inhibition of hemolysis was dose-dependent, and the esters were significantly more effective than gallic acid. Gallic acid and its esters were compared with regard to their reactivity to free radicals, using the DPPH and AAPH/pyranine free-cell assays, and no significant difference was obtained. Gallic acid and its esters not only failed to inhibit the depletion of intracellular GSH in erythrocytes induced by AAPH but exacerbated it. Similarly, the oxidation of GSH by AAPH or horseradish peroxidase/H(2)O(2) in cell-free systems was exacerbated by gallic acid or gallates. This property could be involved in the recent findings on proapoptotic and pro-oxidant activities of gallates in tumor cells. We provide evidence that lipophilicity and not only radical scavenger potency is an important factor regarding the efficiency of antihemolytic substances.Univ Estadual Paulista, UNESP, Fac Ciencias, Dept Quim, BR-17033360 Bauru, SP, BrazilUniv Estadual Paulista, UNESP, Fac Ciencias Farmaceut, Dept Anal Clin, Araraquara, SP, BrazilUniv Estadual Paulista, UNESP, Inst Quim, Dept Quim Organ, Araraquara, SP, BrazilUniv Estadual Paulista, UNESP, Fac Ciencias, Dept Quim, BR-17033360 Bauru, SP, BrazilUniv Estadual Paulista, UNESP, Fac Ciencias Farmaceut, Dept Anal Clin, Araraquara, SP, BrazilUniv Estadual Paulista, UNESP, Inst Quim, Dept Quim Organ, Araraquara, SP, Brazi