Anacardic acid derivatives as inhibitors of glyceraldehyde-3-phosphate dehydrogenase from Trypanosoma cruzi

Pereira, Junia M.; Severino, Richele P.; Vieira, Paulo C.; Fernandes, João B.; Silva, Maria Fátima das Graças Fernandes da; Zottis, Aderson; Andricopulo, Adriano D.; Oliva, Glaucius; Corrêa, Arlene G.

doi:10.1016/j.bmc.2008.08.057

Cited by 55 publications

(37 citation statements)

References 37 publications

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“…Anacardic acid is already being used as a template for initial drug discovery research against a number of interesting targets, including the use of derivatives of anacardic acid as inhibitors of glyceraldehyde-3-phosphate dehydrogenase from the Trypanosoma cruzi pathogen that causes Chagas disease (Pereira et al, 2008). Several studies have focused on analogs of anacardic acid being used as antibacterial agents against methicillin-resistant S. aureus (Green et al, 2007), against Mycobacterium smegmatis and Mycobacterium tuberculosis (Swamy et al, 2007), and against Streptococcus mutans (Green et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Anacardic Acid Inhibits the Catalytic Activity of Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9

Omanakuttan

Nambiar

Harris³

et al. 2012

Mol Pharmacol

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Cashew nut shell liquid (CNSL) has been used in traditional medicine for the treatment of a wide variety of pathophysiological conditions. To further define the mechanism of CNSL action, we investigated the effect of cashew nut shell extract (CNSE) on two matrix metalloproteinases, MMP-2/gelatinase A and MMP-9/gelatinase B, which are known to have critical roles in several disease states. We observed that the major constituent of CNSE, anacardic acid, markedly inhibited the gelatinase activity of 3T3-L1 cells. Our gelatin zymography studies on these two secreted gelatinases, present in the conditioned media from 3T3-L1 cells, established that anacardic acid directly inhibited the catalytic activities of both MMP-2 and MMP-9. Our docking studies suggested that anacardic acid binds into the MMP-2/9 active site, with the carboxylate group of anacardic acid chelating the catalytic zinc ion and forming a hydrogen bond to a key catalytic glutamate side chain and the C15 aliphatic group being accommodated within the relatively large S1Ј pocket of these gelatinases. In agreement with the docking results, our fluorescence-based studies on the recombinant MMP-2 catalytic core domain demonstrated that anacardic acid directly inhibits substrate peptide cleavage in a dosedependent manner, with an IC 50 of 11.11 M. In addition, our gelatinase zymography and fluorescence data confirmed that the cardol-cardanol mixture, salicylic acid, and aspirin, all of which lack key functional groups present in anacardic acid, are much weaker MMP-2/MMP-9 inhibitors. Our results provide the first evidence for inhibition of gelatinase catalytic activity by anacardic acid, providing a novel template for drug discovery and a molecular mechanism potentially involved in CNSL therapeutic action.

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Section: Discussionmentioning

confidence: 99%

Anacardic Acid Inhibits the Catalytic Activity of Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9

Omanakuttan

Nambiar

Harris³

et al. 2012

Mol Pharmacol

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“…Biological and pharmacological investigations carried out on these anacardic acids revealed numerous interesting activities such as parasiticidal (Cui et al, 2008;Pereira et al, 2008), anti-staphylococcus aureus (Kubo et al, 2003), anti-Helicobacter pylori (Castillo-Juárez et al, 2007), antioxidant (Trevisan et al, 2006), lipoxygenase inhibition (Kubo et al, 2008) and inhibition of NF-ĸB (Nuclear Factor kappa B) (Sung et al, 2008).…”

Section: Anadenanthera Colubrina (Vell) Brenan Fabaceae (Angico-bramentioning

confidence: 99%

Bioactivity and potential therapeutic benefits of some medicinal plants from the Caatinga (semi-arid) vegetation of Northeast Brazil: a review of the literature

Silva¹,

Melo²,

Vasconcelos³

et al. 2012

Rev. bras. farmacogn.

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Abstract:Medicinal plants have been used in traditional medicine for several thousand years all over the world. In this sense, information from Brazilian ethnic groups on folk medicine have contributed to the discovery of pharmacological activities from various plant-derived agents potentially leading to the innovative drugs. The Caatinga (semi-arid) vegetation is a highly threatened biome, covering a vast area in northeastern Brazil and has suffered from strong human influence for many decades. Many plants species found in the Caatinga have been widely used in folk medicine and for commercial manufacturing of phytotherapeutic products. Thus, the present review aims to disseminate to the scientific community some known species of medicinal plants found in the Caatinga that have been studied and analyzed in pharmacological scientific assays. Among the species that stood out for their local importance and multiplicity of uses were: Amburana cearensisand Zingiber officinalis L. (gengibre). The present study shows that several herbal constituents from Caatinga plants, whose pharmacological actions have been well characterized, may be relevant candidates for future and innovative therapeutic development.

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“…Therefore, the vital dependence on glycolysis as the main source of energy for the parasites, combined to distinct molecular properties when compared with their human counterparts makes the glycolytic enzymes attractive targets for drug design. Structure-and ligand-based approa- ches on enzymes of the carbohydrate metabolism pathway have identified several promising inhibitors, as well as shed light on the structural basis for selective inhibition [102][103][104][105][106][107][108][109][110][111][112][113][114][115][116][117].…”

Section: Phosphofructokinase and Pyruvate Kinase Inhibitorsmentioning

confidence: 99%

Structure-Based Drug Discovery for Tropical Diseases

Güido

Oliva

2009

CTMC

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Parasitic diseases are amongst the foremost threats to human health and welfare around the world. In tropical and subtropical regions of the world, the consequences of parasitic infections are devastating both in terms of human morbidity and mortality. The current available drugs are limited, ineffective, and require long treatment regimens. To overcome these limitations, the identification of new macromolecular targets and small-molecule modulators is of utmost importance. The advances in genomics and proteomics have prompted drug discovery to move toward more rational strategies. The increasing understanding of the fundamental principles of protein-ligand interactions combined with the availability of compound libraries has facilitated the identification of promising hits and the generation of high quality lead compounds for tropical diseases. This review presents the current progresses and applications of structure-based drug design (SBDD) for the discovery of innovative chemotherapy agents for a variety of parasitic diseases, highlighting the challenges, limitations, and future perspectives in medicinal chemistry.

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Anacardic acid derivatives as inhibitors of glyceraldehyde-3-phosphate dehydrogenase from Trypanosoma cruzi

Cited by 55 publications

References 37 publications

Anacardic Acid Inhibits the Catalytic Activity of Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9

Anacardic Acid Inhibits the Catalytic Activity of Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9

Bioactivity and potential therapeutic benefits of some medicinal plants from the Caatinga (semi-arid) vegetation of Northeast Brazil: a review of the literature

Structure-Based Drug Discovery for Tropical Diseases

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