Organoselenocyanates and symmetrical diselenides redox modulators: Design, synthesis and biological evaluation

Shaaban, Saad; Negm, Amr; Sobh, Mohamed; Wessjohann, Ludger A.

doi:10.1016/j.ejmech.2015.05.002

Cited by 83 publications

(49 citation statements)

References 78 publications

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“…Taking into account the results related to activity and selectivity and considering our exigent criteria for both parameters (ED 50 of Ͻ2.5 M and SI of Ͼ25), four derivatives, one selenocyanate, 1h, and two diselenides (2d and 2e) were selected for further studies. Despite the fact that compound 2f fulfilled these criteria, it could not be tested due to solubility problems.…”

Section: Discussionmentioning

confidence: 99%

“…The synthesis of compounds 1a to 1o was carried out according to the procedure described in the literature (48)(49)(50), with a few modifications. Briefly, KSeCN (4 mmol) was added to a solution of the appropriate halyl derivative (4 mmol) in acetone (50 ml) and the mixture was heated under reflux for 2 to 4 h. The resulting precipitate (KBr) was filtered off.…”

Section: Methodsmentioning

confidence: 99%

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Novel Heteroaryl Selenocyanates and Diselenides as Potent Antileishmanial Agents

Baquedano

Alcolea

Toro

et al. 2016

Antimicrob Agents Chemother

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A series of new selenocyanates and diselenides bearing interesting bioactive scaffolds (quinoline, quinoxaline, acridine, chromene, furane, isosazole, etc.) was synthesized, and their in vitro leishmanicidal activities against Leishmania infantum amastigotes along with their cytotoxicities in human THP-1 cells were determined. Interestingly, most tested compounds were active in the low micromolar range and led us to identify four lead compounds (1h, 2d, 2e, and 2f) with 50% effective dose (ED 50 ) values ranging from 0.45 to 1.27 M and selectivity indexes of >25 for all of them, much higher than those observed for the reference drugs. These active derivatives were evaluated against infected macrophages, and in order to gain preliminary knowledge about their possible mechanism of action, the inhibition of trypanothione reductase (TryR) was measured. Among these novel structures, compounds 1h (3,5-dimethyl-4-isoxazolyl selenocyanate) and 2d [3,3=-(diselenodiyldimethanediyl)bis(2-bromothiophene)] exhibited good association between TryR inhibitory activity and antileishmanial potency, pointing to 1h, for its excellent theoretical ADME (absorption, distribution, metabolism, and excretion) properties, as the most promising lead molecule for leishmancidal drug design.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Novel Heteroaryl Selenocyanates and Diselenides as Potent Antileishmanial Agents

Baquedano

Alcolea

Toro

et al. 2016

Antimicrob Agents Chemother

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“…The results obtained for the reference drug, meglumine antimonate, were included in all cases for comparison. Biological data evidenced that half of the screened compounds (compounds 8,9,10,11,13,15,17,18,20,21,24,26,29,33,35,37,38,42,43,44,45,46, 47, and 48) showed high levels of bioactivity against L. infantum, presenting greater potency than the reference drug, meglumine antimonate, against both forms (IC 50 s, 18.0 M for promastigotes and 24.2 M for amastigotes).…”

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confidence: 99%

Library of Seleno-Compounds as Novel Agents against Leishmania Species

Martín‐Montes

Plano

Martín‐Escolano

et al. 2017

Antimicrob Agents Chemother

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The in vitro leishmanicidal activities of a series of 48 recently synthesized selenium derivatives against Leishmania infantum and Leishmania braziliensis parasites were tested using promastigotes and intracellular amastigote forms. The cytotoxicity of the tested compounds for J774.2 macrophage cells was also measured in order to establish their selectivity. Six of the tested compounds (compounds 8, 10, 11, 15, 45, and 48) showed selectivity indexes higher than those of the reference drug, meglumine antimonate (Glucantime), for both Leishmania species; in the case of L. braziliensis, compound 20 was also remarkably selective. Moreover, data on infection rates and amastigote numbers per macrophage showed that compounds 8, 10, 11, 15, 45, and 48 were the most active against both Leishmania species studied. The observed changes in the excretion product profile of parasites treated with these six compounds were also consistent with substantial cytoplasmic alterations. On the other hand, the most active compounds were potent inhibitors of Fe superoxide dismutase (Fe-SOD) in the two parasite species considered, whereas their impact on human CuZn-SOD was low. The high activity, low toxicity, stability, low cost of the starting materials, and straightforward synthesis make these compounds appropriate molecules for the development of affordable antileishmanicidal agents.KEYWORDS Leishmania, selenium, superoxide dismutase, glucose metabolism L eishmaniasis, caused by the intracellular protozoan Leishmania, is transmitted by the bite of phlebotomine sand flies and is endemic in 98 countries, with over 350 million people being at risk (1). Environmental, demographic, and human behavioral factors and coinfections contribute to the changing epidemiology of the disease and to its recent worldwide spread. Clinical manifestations are divided into visceral leishmaniasis (VL; or kala-azar) (2) and the forms cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (ML). CL remains the most common form of leishmaniasis both in general and in international travelers (3-5).The drugs available for the treatment of VL and severe CL include pentavalent antimonials (SbV), deoxycholate, amphotericin B (AMB), and miltefosine (MIL), all of which have high levels of toxicity and/or require long-duration treatment schedules (5, 6). Moreover, with the exception of MIL, all these drugs must be administered by the parenteral route (7).In the last decade, resistance to SbV has increased mainly due to low rates of compliance with the treatment schedule. In areas where the parasites are resistant to

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“…The deep violet radical 1,1‐diphenyl‐2‐picryl‐hydrazine was formed by the reaction of antioxidants with DPPH. The former had a strong absorption band at 517 nm . The assay relied on the absorption disappearance and decolorization due to electron pairing in the presence of free radical scavengers.…”

Section: Resultsmentioning

confidence: 99%

Bis‐dioxomolybdenum (VI) oxalyldihydrazone complexes: Synthesis, characterization, DFT studies, catalytic epoxidation potential, molecular modeling and biological evaluations

Adam

Ahmed

Elhady

et al. 2020

Applied Organom Chemis

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Two cis‐bis‐dioxomolybdenum oxalylsalicylidenedihydrazone complexes (MoO2L1 and MoO2L2) were synthesized via the complexation of dioxomolybdenum (VI) acetylacetonate with oxalylsalicylidenedihydrazone (H2L1) and p‐sodium sulfonate oxalylsalicylidenedihydrazone (H2L2) bis‐Schiff base chelating ligands, respectively. The structures of the newly synthesized complexes were confirmed by 1H‐ and 13C‐NMR, IR, ultraviolet–visible and mass spectra, as well as elemental analyses (EA) and conductivity measurements. The spectrophotometric continuous variation method revealed the formation of 2: 1 (metal: ligand molar ratios). DFT studies were applied for the ligands and their Mo‐chelates. Interestingly, the bis‐MoO2(VI) oxalyldihydrazone complexes showed remarkable catalytic sufficiency towards the selective (ep)oxidation of 1,2‐cyclooctene, benzyl alcohol and thiophene using H2O2 or tert‐butyl hydroperoxide (tBuOOH) at 85 °C. Under aqueous conditions, the MoO2L2 (with p‐sodium sulfonate substituent) exhibited superior that of the MoO2L1 (without p‐NaSO3―group), highlighting the role of sodium sulfonate substituent in the catalytic progress of the Mo‐chelate. The ligands (H2L1 and H2L2) and their corresponding Mo‐complexes (MoO2L1 and MoO2L2) were assessed for their antitumor and antimicrobial activities. Furthermore, the antioxidant activity was also evaluated using the 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) and superoxide dismutase (SOD) assays. The binding nature between the Mo‐complexes and calf thymus DNA (ctDNA) was also studied within spectroscopic and hydrodynamic techniques.

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Organoselenocyanates and symmetrical diselenides redox modulators: Design, synthesis and biological evaluation

Cited by 83 publications

References 78 publications

Novel Heteroaryl Selenocyanates and Diselenides as Potent Antileishmanial Agents

Novel Heteroaryl Selenocyanates and Diselenides as Potent Antileishmanial Agents

Library of Seleno-Compounds as Novel Agents against Leishmania Species

Bis‐dioxomolybdenum (VI) oxalyldihydrazone complexes: Synthesis, characterization, DFT studies, catalytic epoxidation potential, molecular modeling and biological evaluations

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