Quercetin pentaacetate inhibits in vitro human respiratory syncytial virus adhesion.

Made available in DSpace on 2020-12-12T01:06:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-15 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Human respiratory syncytial virus (hRSV) is one of the main etiological agents of diseases of the lower respiratory tract and is often responsible for the hospitalization of children and the elderly. To date, treatments are only palliative and there is no vaccine available. Natural products show exceptional structural diversity and they have played a vital role in drug research. Several investigations focused on applied structural modification of natural products to improved metabolic stability, solubility and biological actions them. Quercetin is a flavonoid that presents several biological activities, including anti-hRSV role. Some works criticize the pharmacological use of Quercetin because it has low solubility and low specificity. In this sense, we acetylated Quercetin structure and we used in vitro and in silico assays to compare anti-hRSV function between Quercetin (Q0) and its derivative molecule (Q1). Q1 shows lower cytotoxic effect than Q0 on HEp-2 cells. In addition, Q1 was more efficient than Q0 to protect HEp-2 cells infected with different multiplicity of infection (0.1–1 MOI). The virucidal effects of Q0 and Q1 suggest interaction between these molecules and viral particle. Dynamic molecular results suggest that Q0 and Q1 may interact with F-protein on hRSV surface in an important region to adhesion and viral infection. Q1 interaction with F-protein showed ΔG= -14.22 kcal/mol and it was more stable than Q0. Additional, MTT and plate assays confirmed that virucidal Q1 effects occurs during adhesion step of cycle hRSV replication. In conclusion, acetylation improves anti-hRSV Quercetin effects because Quercetin pentaacetate could interact with F-protein with lower binding energy and better stability to block viral adhesion. These results show alternative anti-hRSV strategy and contribute to drug discovery and development. Universidade Estadual Paulista UNESP (FCLAssis) Universidade Estadual Paulista UNESP IBILCE Centro Multiusuário de Inovação Biomolecular (CMIB) Universidade Estadual Paulista UNESP IBILCE Department of Biology University of Rome Tor Vergata, Via della Ricerca Scientifica 1 Universidade Estadual Paulista UNESP (FCLAssis) Universidade Estadual Paulista UNESP IBILCE Centro Multiusuário de Inovação Biomolecular (CMIB) Universidade Estadual Paulista UNESP IBILCE FAPESP: 2014/12298-

Antifungal Activity of Decyl Gallate against Several Species of Pathogenic Fungi

This work aims to demonstrate that the gallic acid structure modification to the decyl gallate (G14) compound contributed to increase the antifungal activity against several species of pathogenic fungi, mainly, Candida spp., Cryptococcus spp., Paracoccidioides spp., and Histoplasma capsulatum, according to standardized microdilution method described by Clinical Laboratory Standard Institute (CLSI) documents. Moreover this compound has a particularly good selectivity index value, which makes it an excellent candidate for broad-spectrum antifungal prototype and encourages the continuation of subsequent studies for the discovery of its mechanism of action

Estudo químico de Pterogyne nitens (Caesalpinioideae), síntese e potencial farmacológico de alcalóides guanidínicos e análogos

O estudo fitoquímico dos caules, folhas, frutos e flores de Pterogyne nitens (Caesalpinioideae) forneceu cinco substâncias inéditas: nitensidina D (42), nitensidina E (43), nitensosídeo A (45), nitensosídeo B (47), pteroginosídeo (51) e 19 substâncias conhecidas, pteroginina (1), pteroginidina (2), pedalina (7), sorbifolina (44), pedalitina (46), kaempferol (48), afzelina (49), kaempferitrina (50), quercetina (52), isoquercitrina (53), rutina (54), quercetina 3-O-soforosídeo (55), taxifolina (61), astilbina (62), ourateacatequina (63) e os ácidos cafeico (56), ferúlico (57), sinápico (58), clorogênico (59) e gálico (60) . Todos os flavonóis e flavonas foram submetidos ao ensaio bioquímico com mieloperoxidase (MPO). De maneira geral, os flavonóides com padrão catecólico no anel B mostraram maior efeito inibitório sobre a MPO que os 4’-hidroxi-flavonóides. Os flavonóides mais ativos, 46, 52, 53, 54, e 55 exibiram valores de CI50 de 3,75, 1,22, 3,75, 3,60 e 3,72 nM, respectivamente. Adicionalmente, a capacidade seqüestradora de radicais dos flavonóis e flavonas foi avaliada sobre os radicais ABTS e DPPH. Os alcalóides guanidínicos de P. nitens foram selecionados como modelos para o planejamento e síntese de análogos antitumorais e antifúngicos. Uma série de 24 substâncias sintéticas, incluindo guanidinas mono e dissubstituídas, e seus bioisósteros foi preparada empregando-se protocolos descritos na literatura com pequenas modificações. Os derivados guanidínicos sintéticos e seus análogos foram avaliados em quatro linhagens de células tumorais e nove cepas fúngicas. Os estudos de relação estrutura-atividade qualitativa foram concentrados sobre duas regiões das estruturas moleculares dos alcalóides: o núcleo guanidínico e a cadeia...The phytochemical study of the stems, leaves, fruits and flowers of Pterogyne nitens (Caesalpinioideae) furnished five new compounds: nitensidine D (42), nitensidine E (43), nitensoside A (45), nitensoside B (47), pterogynoside (51), and 19 known compounds, pterogynine (1), pterogynidine (2), pedalin (7), sorbifolin (44), pedalitin (46), kaempferol (48), afzelin (49), kaempferitrin (50), quercetin (52), isoquercitrin (53), rutin (54), quercetin 3-O-sophoroside (55), taxifolin (61), astilbin (62), ourateacatechin (63) and caffeic (56), ferulic (57), sinapic (58), chlorogenic (59) and gallic (60) acids. All flavonols and flavones were evaluated for their myeloperoxidase (MPO) inhibitory activity. In general, flavonoids that posses the ring B with a cathecol pattern are shown to display a major inhibitory effect on MPO than 4’-hydroxyl-flavonoids. The flavonoids, 46, 52, 53, 54, and 55 were active, and exhibited IC50 values of 3,75, 1,22, 3,75, 3,60 and 3,72 nM, respectively. Additionally, the radical scavengers of the flavones and flavonols was evaluated towards ABTS and DPPH. The guanidine alkaloids from P. nitens were selected as prototype compounds for antitumor and antifungal analogue design, and a series of 24 synthetic compounds (mono and disubstituted guanidines with isoprenyl, geranyl or farnesyl groups, and bioisosters) have been prepared using synthetic protocols previously described with minor modifications. The guanidine derivatives and their analogues were evaluated towards four cancer cell lines and nine human pathogenic fungi strains. The qualitative structure-activity relationship studies were concentrated on two regions of the molecular structures of the alkaloids: at the guanidine nucleus and at the prenyl side chain. Preliminary observations on the synthetic guanidine structural features, and their biological activity could... (Complete abstract click electronic access below)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Estudo químico de Pterogyne nitens (Caesalpinioideae), síntese e potencial farmacológico de alcalóides guanidínicos e análogos

O estudo fitoquímico dos caules, folhas, frutos e flores de Pterogyne nitens (Caesalpinioideae) forneceu cinco substâncias inéditas: nitensidina D (42), nitensidina E (43), nitensosídeo A (45), nitensosídeo B (47), pteroginosídeo (51) e 19 substâncias conhecidas, pteroginina (1), pteroginidina (2), pedalina (7), sorbifolina (44), pedalitina (46), kaempferol (48), afzelina (49), kaempferitrina (50), quercetina (52), isoquercitrina (53), rutina (54), quercetina 3-O-soforosídeo (55), taxifolina (61), astilbina (62), ourateacatequina (63) e os ácidos cafeico (56), ferúlico (57), sinápico (58), clorogênico (59) e gálico (60) . Todos os flavonóis e flavonas foram submetidos ao ensaio bioquímico com mieloperoxidase (MPO). De maneira geral, os flavonóides com padrão catecólico no anel B mostraram maior efeito inibitório sobre a MPO que os 4’-hidroxi-flavonóides. Os flavonóides mais ativos, 46, 52, 53, 54, e 55 exibiram valores de CI50 de 3,75, 1,22, 3,75, 3,60 e 3,72 nM, respectivamente. Adicionalmente, a capacidade seqüestradora de radicais dos flavonóis e flavonas foi avaliada sobre os radicais ABTS e DPPH. Os alcalóides guanidínicos de P. nitens foram selecionados como modelos para o planejamento e síntese de análogos antitumorais e antifúngicos. Uma série de 24 substâncias sintéticas, incluindo guanidinas mono e dissubstituídas, e seus bioisósteros foi preparada empregando-se protocolos descritos na literatura com pequenas modificações. Os derivados guanidínicos sintéticos e seus análogos foram avaliados em quatro linhagens de células tumorais e nove cepas fúngicas. Os estudos de relação estrutura-atividade qualitativa foram concentrados sobre duas regiões das estruturas moleculares dos alcalóides: o núcleo guanidínico e a cadeia...The phytochemical study of the stems, leaves, fruits and flowers of Pterogyne nitens (Caesalpinioideae) furnished five new compounds: nitensidine D (42), nitensidine E (43), nitensoside A (45), nitensoside B (47), pterogynoside (51), and 19 known compounds, pterogynine (1), pterogynidine (2), pedalin (7), sorbifolin (44), pedalitin (46), kaempferol (48), afzelin (49), kaempferitrin (50), quercetin (52), isoquercitrin (53), rutin (54), quercetin 3-O-sophoroside (55), taxifolin (61), astilbin (62), ourateacatechin (63) and caffeic (56), ferulic (57), sinapic (58), chlorogenic (59) and gallic (60) acids. All flavonols and flavones were evaluated for their myeloperoxidase (MPO) inhibitory activity. In general, flavonoids that posses the ring B with a cathecol pattern are shown to display a major inhibitory effect on MPO than 4’-hydroxyl-flavonoids. The flavonoids, 46, 52, 53, 54, and 55 were active, and exhibited IC50 values of 3,75, 1,22, 3,75, 3,60 and 3,72 nM, respectively. Additionally, the radical scavengers of the flavones and flavonols was evaluated towards ABTS and DPPH. The guanidine alkaloids from P. nitens were selected as prototype compounds for antitumor and antifungal analogue design, and a series of 24 synthetic compounds (mono and disubstituted guanidines with isoprenyl, geranyl or farnesyl groups, and bioisosters) have been prepared using synthetic protocols previously described with minor modifications. The guanidine derivatives and their analogues were evaluated towards four cancer cell lines and nine human pathogenic fungi strains. The qualitative structure-activity relationship studies were concentrated on two regions of the molecular structures of the alkaloids: at the guanidine nucleus and at the prenyl side chain. Preliminary observations on the synthetic guanidine structural features, and their biological activity could... (Complete abstract click electronic access below)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Estudo químico de Pterogyne nitens (Caesalpinioideae), síntese e potencial farmacológico de alcalóides guanidínicos e análogos

O estudo fitoquímico dos caules, folhas, frutos e flores de Pterogyne nitens (Caesalpinioideae) forneceu cinco substâncias inéditas: nitensidina D (42), nitensidina E (43), nitensosídeo A (45), nitensosídeo B (47), pteroginosídeo (51) e 19 substâncias conhecidas, pteroginina (1), pteroginidina (2), pedalina (7), sorbifolina (44), pedalitina (46), kaempferol (48), afzelina (49), kaempferitrina (50), quercetina (52), isoquercitrina (53), rutina (54), quercetina 3-O-soforosídeo (55), taxifolina (61), astilbina (62), ourateacatequina (63) e os ácidos cafeico (56), ferúlico (57), sinápico (58), clorogênico (59) e gálico (60) . Todos os flavonóis e flavonas foram submetidos ao ensaio bioquímico com mieloperoxidase (MPO). De maneira geral, os flavonóides com padrão catecólico no anel B mostraram maior efeito inibitório sobre a MPO que os 4’-hidroxi-flavonóides. Os flavonóides mais ativos, 46, 52, 53, 54, e 55 exibiram valores de CI50 de 3,75, 1,22, 3,75, 3,60 e 3,72 nM, respectivamente. Adicionalmente, a capacidade seqüestradora de radicais dos flavonóis e flavonas foi avaliada sobre os radicais ABTS e DPPH. Os alcalóides guanidínicos de P. nitens foram selecionados como modelos para o planejamento e síntese de análogos antitumorais e antifúngicos. Uma série de 24 substâncias sintéticas, incluindo guanidinas mono e dissubstituídas, e seus bioisósteros foi preparada empregando-se protocolos descritos na literatura com pequenas modificações. Os derivados guanidínicos sintéticos e seus análogos foram avaliados em quatro linhagens de células tumorais e nove cepas fúngicas. Os estudos de relação estrutura-atividade qualitativa foram concentrados sobre duas regiões das estruturas moleculares dos alcalóides: o núcleo guanidínico e a cadeia...The phytochemical study of the stems, leaves, fruits and flowers of Pterogyne nitens (Caesalpinioideae) furnished five new compounds: nitensidine D (42), nitensidine E (43), nitensoside A (45), nitensoside B (47), pterogynoside (51), and 19 known compounds, pterogynine (1), pterogynidine (2), pedalin (7), sorbifolin (44), pedalitin (46), kaempferol (48), afzelin (49), kaempferitrin (50), quercetin (52), isoquercitrin (53), rutin (54), quercetin 3-O-sophoroside (55), taxifolin (61), astilbin (62), ourateacatechin (63) and caffeic (56), ferulic (57), sinapic (58), chlorogenic (59) and gallic (60) acids. All flavonols and flavones were evaluated for their myeloperoxidase (MPO) inhibitory activity. In general, flavonoids that posses the ring B with a cathecol pattern are shown to display a major inhibitory effect on MPO than 4’-hydroxyl-flavonoids. The flavonoids, 46, 52, 53, 54, and 55 were active, and exhibited IC50 values of 3,75, 1,22, 3,75, 3,60 and 3,72 nM, respectively. Additionally, the radical scavengers of the flavones and flavonols was evaluated towards ABTS and DPPH. The guanidine alkaloids from P. nitens were selected as prototype compounds for antitumor and antifungal analogue design, and a series of 24 synthetic compounds (mono and disubstituted guanidines with isoprenyl, geranyl or farnesyl groups, and bioisosters) have been prepared using synthetic protocols previously described with minor modifications. The guanidine derivatives and their analogues were evaluated towards four cancer cell lines and nine human pathogenic fungi strains. The qualitative structure-activity relationship studies were concentrated on two regions of the molecular structures of the alkaloids: at the guanidine nucleus and at the prenyl side chain. Preliminary observations on the synthetic guanidine structural features, and their biological activity could... (Complete abstract click electronic access below)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

In vitro antibacterial activity of prenylated guanidine alkaloids from Pterogyne nitens and synthetic analogues

The present investigation deals with the antibiotic activity of eight natural guanidine alkaloids and two synthetic analogues against a variety of clinically relevant methicillin-resistant Staphylococcus aureus strains. Galegine (1) and pterogynidine (2) were the most potent compounds, with a minimum inhibitory concentration of 4 mg/L, to all tested strains. The preliminary chemical features correlating to anti-MRSA activity showed that the size of the side chain and the substitution pattern in the guanidine core played a key role in the antibacterial activity of the imino group. Guanidine alkaloids 1 and 2 are promising molecular models for further synthetic derivatives and, thus, for medicinal chemistry studies

Antiangiogenic alkaloids from plants

Angiogenesis, the formation of new blood vessels from preexisting capillaries, is an important research field. As the understanding of this process increases, this new knowledge will have a significant impact on several angiogenesisdependent diseases. A wide variety of plants are rich in alkaloids, and these compounds have traditionally been of interest due to their pronounced effects on various physiological activities in animals and humans. Nowadays, it is known that many alkaloids obtained from plants exhibit antiangiogenic activity, and these alkaloids may act through different mechanisms to inhibit angiogenesis. Herein, we will discuss the most important alkaloids obtained from plants, focusing especially in their antiangiogenic activity. Because of the great diversity of plants, certainly, there are many antiangiogenic alkaloids that have yet to be discovered.Hematology and Hemotherapy Center School of Medical Sciences University of Campinas–UNICAMPDepartment of Organic Chemistry Araraquara Institute of Chemistry São Paulo State University–UNESPDepartment of Biochemistry (U38/FCT) Faculty of Medicine University of PortoDepartment of Organic Chemistry Araraquara Institute of Chemistry São Paulo State University–UNES

IDENTIFICATION OF TRITERPENES AND STEROLS FROM PTEROGYNE NITENS (FABACEAE-CAESALPINIOIDEAE) USING HIGH-RESOLUTION GAS CHROMATOGRAPHY

As part of our ongoing bioprospecting studies on secondary metabolites in plants of Cerrado and Atlantic Rain Forest of São Paulo State (Brazil), we describe the identification of triterpenes and sterols present in the hexane extracts and foliar epicuticular wax of Pterogyne nitens Tulasne (Fabaccae-Caesalpinioideae) using high resolution gas chromatography. Compounds detected in these extracts include beta-amyrin (1), taraxerol acetate (2), lupenone (3), beta-amlyrenone (4), germanicone (5), campesterol (6), stigmasterol (7), and beta-sitosterol (8). The method reported herein is shown to be a rapid, sensitive and reproducible tool for describing triterpenes and sterols present in non-polar extracts

Trypanocidal activity of Piper arboreum and Piper tuberculatum (Piperaceae)

In the scope of our ongoing research on bioactive agents from Brazilian flora, twenty-four extracts and fractions obtained from Piper arboreum Aub. and Piper tuberculatum Jacq. (Piperaceae) were screened for trypanocidal activity by using MTT colorimetric assay. The strongest activity was found in hexane fractions from the leaves of P. arboreum (IC50= 13.3 µg/ mL) and P. tuberculatum (IC50 = 17.2 µg/mL). Hexane fractions of the fruits of P. tuberculatum and P. arboreum showed potent toxic effects on epimastigote forms of Trypanosoma cruzi, with values of IC50 (µg/mL) of 32.2 and 31.3, respectively. Additionally, the phytochemical study of the hexane fraction of P. arboreum leaves furnished two pyrrolidine amides, piperyline (1) and 4,5-dihydropiperyline (2), which could be responsible, at least in part for the observed antiprotozoal activity