Aryl piperazine and pyrrolidine as antimalarial agents. Synthesis and investigation of structure–activity relationships

Mendoza, Adela; Pérez‐Silanes, Silvia; Quiliano, Miguel; Pabón, Adriana; Galiano, Silvia; González, Germán; Garavito, Giovanny; Zimic, Mirko; Vaisberg, Abraham; Aldana, Ignacio; Monge, Antonio; Deharo, Eric

doi:10.1016/j.exppara.2011.02.025

Cited by 39 publications

(36 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…14,15 In this context we decided to screen our in-house chemical laboratory library with the purpose of searching drugs against of CD. [16][17][18][19][20][21] We found some arylamine Mannich base derivatives tested before for their in vitro affinity at the 5-HT transporter and 5HT 1A receptors 17 or 5-HT 7 20 receptors as potential antidepressants and against Plasmodium falciparum as a potential antimalarials 19 and in every case they were not active. However risk of potential off-target activities derived from a possible CSN activity is unlikely.…”

Section: Introductionmentioning

confidence: 99%

In Vitro and in Vivo Anti-Trypanosoma cruzi Activity of New Arylamine Mannich Base-Type Derivatives

et al. 2016

Self Cite

View full text Add to dashboard Cite

ABSTRACT. Chagas disease is a neglected tropical disease with 6-7 million people infected worldwide and there is no effective treatment. Therefore, there is an urgent need to continue researching in order to discover novel therapeutic alternatives. We present a series of arylaminoketone derivatives as means of identifying new drugs to treat Chagas disease in the acute phase with greater activity, less toxicity and with a larger spectrum of action than that corresponding to the reference drug benznidazole. Indexes of high selectivity found in vitro formed the basis for later in vivo assays in BALB/c mice. Murine model results show that compounds 3, 4, 7 and 10 induced a remarkable decrease in parasitemia levels in acute phase and the parasitemia reactivation following immunosuppression, and curative rates were higher than with benznidazole. These high anti-parasitic activities encourage us to propose these compounds as promising molecules for developing an easy to synthesize anti-Chagas agent.

show abstract

Section: Introductionmentioning

confidence: 99%

In Vitro and in Vivo Anti-Trypanosoma cruzi Activity of New Arylamine Mannich Base-Type Derivatives

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…Molecular docking studies also suggested subsites of union to compound (I), situated near the S1', S1 and S3 pockets of the protein. 36 The 4-nitro-2-trifluromethyl phenyl group of this conformation was set close to the S1 and S3 pockets and the 4fluoro-1-naphtyl is located in the vicinity of the S2 pocket.…”

Section: Arylamino Alcohols Derivativesmentioning

confidence: 94%

“…34 Hydroxylpropyl-piperazines derivatives, belonging to this chemical family, have shown outstanding activity against P. falciparum chloroquine-resistant strains. 35,36 According to recent publications, 37,38 arylamino alcohol derivatives could target the Plasmodium plasmepsin II enzyme. This enzyme, of recent interest, is involved in the initial steps of the hemoglobin degradation, which is a critical issue in the intraerythrocytic cycle of the parasite, taking place inside the food vacuole.…”

Section: Arylamino Alcohols Derivativesmentioning

confidence: 99%

“…As a result of the data obtained with this type of molecules, we discovered compounds with a promising profile as antiplasmodial agents. 36 Parallelly, important facts, such as the genome project and advancement of computer technology and techniques within the computer-assisted drug discovery and development (CADDD) discipline, have revolutionized the manner in which public and private laboratories work. Novel techniques or approaches such as absorption, distribution, metabolism, excretion and toxicity (ADMET) prediction, molecular docking, homology modeling, and molecular dynamics, among others, are currently part of the routine procedures in several drug discovery groups.…”

Section: Arylamino Alcohols Derivativesmentioning

confidence: 99%

See 1 more Smart Citation

Quinoxaline and Arylaminoalcohol Derivatives as Antiplasmodial and Leishmanicidal Agents: A Review of our First Ten Years in the Field

Quiliano¹,

Aldana²

2013

Revista Virtual De Química

Self Cite

View full text Add to dashboard Cite

Resumo: Doenças negligenciadas constituem um grande problema de saúde na atualidade. Contudo, estas doenças não são de interesse para a indústria farmacêutica, uma vez que elas geralmente afetam pessoas de baixo poder aquisitivo. Descrevemos aqui, o trabalho relacionado à malária e à leishmaniose que estamos desenvolvendo ao longo da última década. Nossa experiência neste campo é focada em duas famílias de compostos químicos: derivados de quinoxalina e aril -amino-álcool. Atualmente, esforços estão centralizados na pesquisa de novas entidades químicas, bem como na superação da resistência a compostos antimaláricos. Adicionalmente, entidades químicas relatadas por outros autores e derivados de quinoxalina relacionados são a bordadas. Estas duas doenças são consideradas de extremo interesse científico e social, necessitando tanto de novos fármacos quanto do aperfeiçoamento dos tratamentos existentes. Palavras-chave:Malária; Leishmaniose; Quinoxalina di-N-óxido; Aril-amino-álcool. AbstractsNeglected diseases constitute a great health problem in today's world. However, these diseases are not of interest to the pharmaceutical industry as they generally affect populations of scarce economical resources. Here, we describe the work related to mal aria and leishmaniasis that we have developed over the last ten years. Our experience in the field is focused on two families of chemical compounds: quinoxaline and arylamino alcohol derivatives. Current efforts are centered on researching new chemical entities as well as on overcoming drug resistance to antimalarial compounds. In addition, chemical entities reported by other authors and related quinoxaline derivatives are addressed. These two diseases are considered to be of great scientific and social interest, requiring new drugs so as to achieve improved treatments.

show abstract

“…The IC 50 values (the concentration of sample required to inhibit 50% parasite growth) were calculated by linear interpolation [29][30][31] as follow: …”

Section: In Vitro Antimalarial Activity Assaymentioning

confidence: 99%

Antimalarial activity of HIV-1 protease inhibitor in chromone series

Lerdsirisuk

Maicheen

Ungwitayatorn

2014

Bioorganic Chemistry

View full text Add to dashboard Cite

Aryl piperazine and pyrrolidine as antimalarial agents. Synthesis and investigation of structure–activity relationships

Cited by 39 publications

References 22 publications

In Vitro and in Vivo Anti-Trypanosoma cruzi Activity of New Arylamine Mannich Base-Type Derivatives

In Vitro and in Vivo Anti-Trypanosoma cruzi Activity of New Arylamine Mannich Base-Type Derivatives

Quinoxaline and Arylaminoalcohol Derivatives as Antiplasmodial and Leishmanicidal Agents: A Review of our First Ten Years in the Field

Antimalarial activity of HIV-1 protease inhibitor in chromone series

Contact Info

Product

Resources

About