Novel insights for dihydroorotate dehydrogenase class 1A inhibitors discovery

Cheleski, Juliana; Rocha, Jansle Vieira; Pinheiro, Matheus Pinto; Wiggers, Helton José; Silva, Albérico Borges Ferreira da; Nonato, Maria Cristina; Montanari, Carlos Alberto

doi:10.1016/j.ejmech.2010.09.055

Cited by 54 publications

(46 citation statements)

References 56 publications

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“…The compounds ID71, ID130, and ID195, which are inhibitors of DHODH from T. cruzi were toxic against L. amazonensis promastigotes. The DHODH is a dimeric enzyme that catalyzes the fourth step in the de novo pyrimidine biosynthetic pathway, with one flavin mononucleotide bound to each subunit as a prosthetic group [25]. This is also the fourth and rate-limiting step in the de novo pyrimidine pathway [28].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the active site of DHODH to map structure differences between human, T. cruzi and Leishmania was studied [25]. The metabolic pathways enzymatic system similarity between trypanosomatides [25][26][27] prompted us to assay 17 compounds that are inhibitors designed of different metabolic enzymes with different scaffold and catalytic mechanism against L. amazonensis. Three out of the 17 compounds tested in this study exhibited toxicity against promastigotes.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, some small synthetic molecules developed by virtual screening and isothermal titrating calorimetry have been identified as potent inhibitors of T. cruzi GAPDH and toxic for S. cerevisae and T. cruzi trypomastigotes [14,15]. In addition, the active site of DHODH to map structure differences between human, T. cruzi and Leishmania was studied [25]. The metabolic pathways enzymatic system similarity between trypanosomatides [25][26][27] prompted us to assay 17 compounds that are inhibitors designed of different metabolic enzymes with different scaffold and catalytic mechanism against L. amazonensis.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Evaluation of the leishmanicidal and cytotoxic effects of inhibitors for microorganism metabolic pathway enzymes

Barbosa

Costa

Rocha

et al. 2015

Biomedicine & Pharmacotherapy

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Evaluation of the leishmanicidal and cytotoxic effects of inhibitors for microorganism metabolic pathway enzymes

Barbosa

Costa

Rocha

et al. 2015

Biomedicine & Pharmacotherapy

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“…The extracts of Fucus Evanescense and Babingtonii Pelvetia algae, provided a reduction of up to 59% in activity of DHOD [143].…”

Section: Other Promising Targetsmentioning

confidence: 99%

New Treatments for Chagas Disease and the Relationship between Chagasic Patients and Cancers

Oliveira¹,

Mendes²,

Almeida³

et al. 2014

CRJ

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Abstract:Chagas disease is an infectious illness with a broad distribution throughout the South American and African continents, importantly influencing human morbidity and mortality and a controversial relationship with the onset of cancers, especially of the gastrointestinal tract system. In addition, it is listed by the World Health Organization (WHO) as one ofthe most neglected tropical diseases. Although Chagas disease (CD) was discovered more than 100 years ago, the existing therapies show low efficacy and serious side effects and developing safer and more effective drugs remains a hard challenge. Thus, this review highlights the main, novel and promising treatments against Trypanosoma cruzi, including biomacromolecules, natural products, vaccines, and metabolic pathway targets and highlights a worsening of esophageal cancer prognosis in chagasic patients. Moreover, we also discuss the perspectives of obtaining original optimized drugs that take advantage of organic and inorganic medicinal chemistry advances, as well as molecular modeling and biotechnology.

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“…O sítio ativo (S1), uma extensão da região S1 (S2), a região atrás do loop catalítico (S3), uma extensão da região S3 (S4) e a região localizada na interface dimérica (S5) estão indicadas em rosa, azul, laranja, verde e vermelho, respectivamente [73].…”

Section: Figuraunclassified

Estudo do mecanismo e inibição da enzima diidroorotato desidrogenase de Leishmania major

Reis¹

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Novel insights for dihydroorotate dehydrogenase class 1A inhibitors discovery

Cited by 54 publications

References 56 publications

Evaluation of the leishmanicidal and cytotoxic effects of inhibitors for microorganism metabolic pathway enzymes

Evaluation of the leishmanicidal and cytotoxic effects of inhibitors for microorganism metabolic pathway enzymes

New Treatments for Chagas Disease and the Relationship between Chagasic Patients and Cancers

Estudo do mecanismo e inibição da enzima diidroorotato desidrogenase de Leishmania major

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