Synthesis and antiproliferative activity of novel symmetrical alkylthio- and alkylseleno-imidocarbamates

Ibáñez, Elena; Plano, Daniel; Font, Marı́a; Calvo, Alfonso; Prior, Celia; Palop, Juan Antonio; Sanmartín, Carmen

doi:10.1016/j.ejmech.2010.11.013

Cited by 58 publications

(32 citation statements)

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“…, and 8b [methyl-N,N=-di (quinolin-3-ylcarbonyl)-imidoselenocarbamate] were synthesized in good yield and purity as previously described by our group (12). Briefly, synthesis started from Se-methyl-imidoselenocarbamate and the corresponding heteroaryl acyl chloride in a 1:2 molar ratio, respectively, in chloroform in the presence of pyridine as a catalyst at room temperature for 48 h. All compounds were characterized by routinely used methods, such as nuclear magnetic resonance (NMR) and infrared (IR) and mass spectrometry (MS).…”

Section: Methodsmentioning

confidence: 99%

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Leishmanicidal Activities of Novel Methylseleno-Imidocarbamates

Fernández-Rubio

Campbell

Vacas

et al. 2015

Antimicrob Agents Chemother

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fThe generation of new antileishmanial drugs has become a priority. Selenium and its derivatives stand out as having promising leishmanicidal activity. In fact, some parasites express selenoproteins and metabolize selenium. Recently, selenium derivatives have shown the potential to reduce parasitemia, clinical manifestations, and mortality in parasite-infected mice. In this paper, after selecting four candidates according to drug similarity parameters, we observed that two of them, called compounds 2b [methyl-N,N=-di(thien-2-ylcarbonyl)-imidoselenocarbamate] and 4b [methyl-N,N=-di(5-nitrothien-3-ylcarbonyl)-imidoselenocarbamate], exhibit low 50% inhibitory concentrations (IC 50 s) (<3 M) and good selectivity indexes (SIs) (>5) in Leishmania major promastigotes and lack toxicity on macrophages. In addition, in analysis of their therapeutic potential against L. major in vitro infection, both compounds display a dramatic reduction of amastigote burden (ϳ80%) with sublethal concentrations. Furthermore, in macrophages, these selenocompounds induce nitric oxide production, which has been described to be critical for defense against intracellular pathogens. Compounds 2b and 4b were demonstrated to cause cell cycle arrest in G 1 . Interestingly, evaluation of expression of genes related to proliferation (PCNA), treatment resistance (ABC transporter and alpha-tubulin), and virulence (quinonoid dihydropteridine reductase [QDPR]) showed several alterations in gene expression profiling. All these results prompt us to propose both compounds as candidates to treat leishmanial infections.

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Section: Methodsmentioning

confidence: 99%

“…More recently, Se has been recognized as an antioxidant, antiviral, antitumoral, and antiparasitic agent (2,10,11). Methylseleno-imidocarbamates have been described to be antiproliferative molecules against several tumor cell lines, to induce cell cycle arrest, and to trigger apoptosis (12).…”

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confidence: 99%

Leishmanicidal Activities of Novel Methylseleno-Imidocarbamates

Fernández-Rubio

Campbell

Vacas

et al. 2015

Antimicrob Agents Chemother

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“…The structures synthesised correspond to molecules with a central nucleus made up of an alkyl imidothiocarbamate (alkyl isothiourea) or alkyl imidoselenocarbamate (alkyl isoselenourea) connected by a carbonyl group on each side to two identical lateral aromatic or heteroaromatic rings mono, bi or polycyclics ( Figure 8). The sulfur and selenium substituents were varied (methyl, ethyl, benzyl and isopropyl) to determine the effect of the alkyl chain length and the ramifications that this has on the activity (Plano et al, 2007, Ibáñez et al, 2011. The best results in PC-3 were obtained for the compound with X = Se, Y = C, R = CH 3 and R' = 4-CH 3 .…”

Section: Structures and Biological Resultsmentioning

confidence: 91%

New Selenoderivatives as Antitumoral Agents

Sanmartín¹,

Palop²,

Romano³

et al. 2011

Prostate Cancer - Original Scientific Reports and Case Studies

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“…During the last five years, our research group reported the promising and potent anticancer effects for several alkylimidothio-and alkylimidoselenocarbamate derivatives [87][88][89]. These compounds showed a remarkable cytotoxic activity in vitro against prostate cancer cells and other several cancer cell lines.…”

Section: Alkylimidothio-and Alkylimidoselenocarbamatesmentioning

confidence: 99%