Structure–activity relationships of novel inhibitors of glyceraldehyde-3-phosphate dehydrogenase

Leitão, Andrei; Andricopulo, Adriano D.; Oliva, Glaucius; Pupo, Mônica Tallarico; Marchi, Anderson A. de; Vieira, Paulo C.; Silva, Maria Fátima das Graças Fernandes da; Ferreira, Vı́tor F.; Souza, Maria Cecília B. V. de; Sá, Marcus M.; Moraes, Valéria R. S.; Montanari, Carlos Alberto

doi:10.1016/j.bmcl.2004.02.025

Cited by 30 publications

(13 citation statements)

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“…Thus, the activity of the studied extract (CFGH) ( Table 1) is probably related to the presence of the active flavones 2 and 3. However, their enzymatic activity were considered weak, particularly in comparison with chalepin, a coumarin isolated from Pilocarpus spicatus (Rutaceae), which reduced the gGAPDH activity by 75 % at 93 mmol/L (IC 50 = 64 mmol/L) (Vieira et al, 2001;Pavão et al, 2002;Menezes et al, 2003;Moraes et al, 2003;Leitão et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Screening of Trypanosoma cruzi glycosomal glyceraldehyde-3-phosphate dehydrogenase enzyme inhibitors

Leite¹,

Ambrozin²,

Castilho³

et al. 2009

Rev. bras. farmacogn.

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RESUMO: "Busca de inibidores da enzima glicossomal gliceraldeído 3-fosfato desidrogenase de Trypanosoma cruzi". Nesse trabalho foi avaliada a atividade inibitória sobre a enzima glicossomal gliceraldeído-3-fosfato desidrogenase de T. cruzi (gGAPDH) de extratos vegetais oriundos de plantas das famílias Meliaceae e Rutaceae, na concentração de 100 mg/mL. Foram testados 46 extratos, dos quais 15 apresentaram atividade inibitória significativa (% AI ≥ 50). A maioria dos extratos de plantas da família Meliaceae (Cedrela fissilis, Cipadessa fruticosa e Trichilia ramalhoi) apresentou grande potencial em inibir a atividade enzimática. O fracionamento do extrato hexânico dos galhos de C. fruticosa permitiu o isolamento de três flavonóides: flavona, 7-metoxiflavona e 3',4',5',5,7-pentametoxiflavona. Os dois últimos foram ativos na inibição da atividade de gGAPDH. Desta forma, as três espécies de Meliaceae testadas podem ser consideradas promissoras na busca de compostos protótipos para o controle da doença de Chagas.Unitermo: Rutaceae, Meliaceae, flavonóides, gGAPDH, Trypanosoma cruzi, inibidores. ABSTRACT:The inhibitory activity of crude extracts of Meliaceae and Rutaceae plants on glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) enzyme from Trypanosoma cruzi was evaluated at 100 mg/mL. Forty-six extracts were tested and fifteen of them showed significant inhibitory activity (IA % ≥ 50). The majority of the assayed extracts of Meliaceae plants (Cedrela fissilis, Cipadessa fruticosa and Trichilia ramalhoi) showed high ability to inhibit the enzymatic activity. The fractionation of the hexane extract from branches of C. fruticosa led to the isolation of three flavonoids: flavone, 7-methoxyflavone and 3',4',5',5,7-pentamethoxyflavone. The two last compounds showed high ability to inhibit the gGAPDH activity. Therefore, the assayed Meliaceae species could be considered as a promising source of lead compounds against Chagas' disease.

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Section: Discussionmentioning

confidence: 99%

Screening of Trypanosoma cruzi glycosomal glyceraldehyde-3-phosphate dehydrogenase enzyme inhibitors

Leite¹,

Ambrozin²,

Castilho³

et al. 2009

Rev. bras. farmacogn.

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“…Quantitative structure-activity relationships (QSAR) have been successfully employed as a valuable tool to assist the design of bioactive compounds of pharmaceutical interest [6][7][8][9][10]. In the present study, we have collected values of IC 50 for a class of potent inhibitors of HIV-1 protease and used the data to create predictive 2D QSAR models employing the hologram QSAR (HQSAR) method [11][12][13][14][15][16].…”

mentioning

confidence: 99%

Hologram Quantitative Structure-Activity Relationships for a Class of Inhibitors of HIV-1 Protease

Ferreira¹,

Leitão²,

Montanari³

et al. 2007

LDDD

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“…The antioxidant enzyme GR fished by C13, C14, and C19 was a target for antimalarial drug development [47]. The target glycosomal glyceraldehyde-3-phosphate dehydrogenase (GAPDH) found by C11 was a target for the development of novel chemotherapeutic agents for the treatment of Chagas disease [48]. Dihydroorotate dehydrogenase (DHODH) retrieved by C5 and C6 was related to both Leishmania infection and Trypanosoma infection [49].…”

Section: Antiparasitic Activitymentioning

confidence: 99%

In silico target fishing and pharmacological profiling for the isoquinoline alkaloids of Macleaya cordata (Bo Luo Hui)

Lei

Peng

et al. 2015

Chin Med

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BackgroundSome isoquinoline alkaloids from Macleaya cordata (Willd). R. Br. (Bo Luo Hui) exhibited antibacterial, antiparasitic, antitumor, and analgesic effects. The targets of these isoquinoline alkaloids are undefined. This study aims to investigate the compound–target interaction network and potential pharmacological actions of isoquinoline alkaloids of M. cordata by reverse pharmacophore database screening.MethodsThe targets of 26 isoquinoline alkaloids identified from M. cordata were predicted by a pharmacophore-based target fishing approach. Discovery Studio 3.5 and two pharmacophore databases (PharmaDB and HypoDB) were employed for the target profiling. A compound–target interaction network of M. cordata was constructed and analyzed by Cytoscape 3.0.ResultsThirteen of the 65 predicted targets identified by PharmaDB were confirmed as targets by HypoDB screening. The targets in the interaction network of M. cordata were involved in cancer (31 targets), microorganisms (12 targets), neurodegeneration (10 targets), inflammation and autoimmunity (8 targets), parasitosis (5 targets), injury (4 targets), and pain (3 targets). Dihydrochelerythrine (C6) was found to hit 23 fitting targets. Macrophage migration inhibitory factor (MIF) hits 15 alkaloids (C1–2, C11–16, C19–25) was the most promising target related to cancer.ConclusionThrough in silico target fishing, the anticancer, anti-inflammatory, and analgesic effects of M. cordata were the most significant among many possible activities. The possible anticancer effects were mainly contributed by the isoquinoline alkaloids as active components.

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Structure–activity relationships of novel inhibitors of glyceraldehyde-3-phosphate dehydrogenase

Cited by 30 publications

References 20 publications

Screening of Trypanosoma cruzi glycosomal glyceraldehyde-3-phosphate dehydrogenase enzyme inhibitors

Screening of Trypanosoma cruzi glycosomal glyceraldehyde-3-phosphate dehydrogenase enzyme inhibitors

Hologram Quantitative Structure-Activity Relationships for a Class of Inhibitors of HIV-1 Protease

In silico target fishing and pharmacological profiling for the isoquinoline alkaloids of Macleaya cordata (Bo Luo Hui)

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