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Leishmaniasis remains a significant global health concern, with current treatments relying on outdated drugs associated with high toxicity, lengthy administration, elevated costs, and drug resistance. Consequently, the urgent need for safer and more effective therapeutic options in leishmaniasis treatment persists. Previous research has highlighted selenium compounds as promising candidates for innovative leishmaniasis therapy. In light of this, a library of 10 selenium-containing diverse compounds was designed and evaluated in this study. These compounds included selenium-substituted indole, coumarin, chromone, oxadiazole, imidazo[1,2-a]pyridine, Imidazo[2,1-b]thiazole, and oxazole, among others. These compounds were screened against Leishmania amazonensis promastigotes and intracellular amastigotes, and their cytotoxicity was assessed in peritoneal macrophages, NIH/3T3, and J774A.1 cells. Among the tested compounds, MRK-106 and MRK-108 displayed the highest potency against L. amazonensis promastigotes with reduced cytotoxicity. Notably, MRK-106 and MRK-108 exhibited IC50 values of 3.97 µM and 4.23 µM, respectively, and most of the tested compounds showed low cytotoxicity in host cells (CC50 > 200 µM). Also, compounds MRK-107 and MRK-113 showed activity against intracellular amastigotes (IC50 18.31 and 15.93 µM and SI 12.55 and 10.92, respectively). In conclusion, the identified selenium-containing compounds hold potential structures as antileishmanial drug candidates to be further explored in subsequent studies. These findings represent a significant step toward the development of safer and more effective therapies for leishmaniasis, addressing the pressing need for novel and improved treatments. [ABSTRACT FROM AUTHOR]

Here we report the design, synthesis and evaluation of dihydropyrimidinones (DHPMs)‐cinnamic acids hybrids as potential anti‐cancer compounds. The synthetic route was successfully performed and the products obtained in good to excellent yields. These compounds were tested against LNCaP and PC‐3 metastatic prostate cancer cells and RWPE‐1 prostate cells. The results indicate that hybridization was effective, since the hybrids were much more cytotoxic than DHPMs and cinnamic acids evaluated separately. Compound 3 a was the most potent hybrid against PC‐3 cells (IC50 of 15.7 μM) and LNCaP cells (IC50 of 11.5 μM) and was further optimized by bioisosterism and molecular simplification strategies leading to three new analogues (5, 7 and 8). Compounds 3 a, 7 and 8 showed an antiproliferative effect against PC‐3 cells without inducing cell death nor cell cycle arrest. The mechanism of action of compound 8 was further investigated. The results indicated that compound 8 inhibits autophagic flux, and this effect could be linked to the antiproliferative activity. Moreover, in silico prediction of some molecular properties related to pharmacokinetics showed that all the hybrids meet the criteria for a drug prototype to have a good absorption and permeation for oral administration. These results highlight the potential use of DHPMs‐cinnamic acids hybrids as antiproliferative agents for further evaluation of the antitumor activity in vivo. [ABSTRACT FROM AUTHOR]

Herein, we report a KIO4‐mediated, sustainable and chemoselective approach for the one‐pot C(sp2)−H bond hydroxymethylation or methylenation of imidazo‐heteroarenes with formaldehyde, generated in situ via the oxidative cleavage of ethylene glycol or glycerol (renewable reagents) through the Malaprade reaction. In the presence of ethylene glycol, a series of 3‐hydroxymethyl‐imidazo‐heteroarenes was obtained in good to excellent yields. These compounds are important intermediates to access pharmaceutical drugs, e.g. Zolpidem. Furthermore, by using glycerol, bis(imidazo[1,2‐a]pyridin‐3‐yl)methane derivatives were selectively obtained in good to excellent yields. [ABSTRACT FROM AUTHOR]

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Two new copper(II) mononuclear complexes (CSe and CS) were synthesized and characterized by the following techniques: X-ray crystallography, elemental analysis, IR, EPR and UV-vis spectroscopies, conductimetric analysis and mass spectrometry. The crystalline structures of both complexes revealed two neutral complexes pentacoordinated with their chalcogenated ligands coordinating to the copper(II) center in a tridentate way with Se, N, Se and S, N, S as donor atoms and two cis-chloro ions completing the coordination structures. The hydrolytic activity in phosphate diester cleavage of CSe and CS was investigated using 2,4-BDNPP as a substrate, and applying the Michealis–Menten approach, giving the kinetics parameters (CSe/CS): kcat (s−1) = 1.17 × 10−4/1.97 × 10−4; KM (mol L−1) = 3.13 × 10−3/5.58 × 10−3. Both complexes also catalyze the oxidation of the 3,5-di-tert-butylcatechol (3,5DTBC) substrate with turnover numbers of 4.32 × 10−2 s−1 for CSe and 4.87 × 10−2 for CS. [ABSTRACT FROM AUTHOR]

DFT calculations performed on amidoaryldiselenides as electrophilic derivatives evidenced the presence of a prevalent Se⋯O weak interaction when selenium is bonded to a Se atom (diselenides), a Br atom (selenenyl bromide) and an O atom (selenenic acid), while for selenenyl iodide derivatives, a prevalent contribution of the Se⋯N interaction was predicted. This in silico observation has been experimentally exploited for the efficient synthesis of a small library of N-substituted benzoisoselenazol-3(2H)-ones and benzoisothiazol-3(2H)-ones considering the pharmacological relevance of ebselen recently reported also as an antiviral agent against Sars-Cov2. [ABSTRACT FROM AUTHOR]

Background: Organoselenium compounds have antimicrobial activity against some bacteria and fungi; furthermore, the antioxidant activity of diselenides has been demonstrated. The aim of the present work was to examine the in vitro minimal inhibitory concentration of a panel of differently substituted diselenides and their effectiveness in inhibiting biofilm formation and dispersing preformed microbial biofilm of Staphylococcus epidermidis, Staphylococcus aureus, Streptococcus pyogenes and Pseudomonas aeruginosa and the yeast Candida albicans, all involved in wound infections. Moreover, the cytotoxicity of the compounds was determined in human dermal fibroblast and keratinocytes. In closing, we tested their direct antioxidant activity. Results: Diselenides showed different antimicrobial activity, depending on the microorganism. All diselenides demonstrated a good antibiofilm activity against S. aureus and S. epidermidis, the compounds camphor diselenide, bis[ethyl-N-(2'-selenobenzoyl) glycinate] and bis[2'-seleno-N-(1-methyl-2-phenylethyl) benzamide] were active against S. pyogenes and C. albicans biofilm while only diselenides 2,2'-diselenidyldibenzoic acid and bis[ethyl-N-(2'-selenobenzoyl) glycinate] were effective against P. aeruginosa. Moreover, the compounds bis[ethyl-N-(2'-selenobenzoyl) glycinate] and bis[2'-seleno-N-(1-methyl-2-phenylethyl) benzamide] showed an antioxidant activity at concentrations lower than the 50 % of cytotoxic concentration. Conclusions: Because microbial biofilms are implicated in chronic infection of wounds and treatment failure, the combination of antimicrobial activity and potential radical scavenging effects may contribute to the improvement of wound healing. Therefore, this study suggests that bis[ethylN-(2'-selenobenzoyl) glycinate] and bis[2'-seleno-N-(1-methyl-2-phenylethyl) benzamide] are promising compounds to be used in preventing and treating microbial wound infections. [ABSTRACT FROM AUTHOR]

The secondary interaction between a polarized chalcogen atom and different Lewis bases, either anionic or neutral, has been studied by charge displacement analysis. Using charge displacement analysis, the charge rearrangement in the adduct upon the formation of the interaction has been quantified and described in great detail. By comparing the theoretical results with the experimental association constants, two linear correlations can be found for anionic and neutral bases. Such correlations can be used to reliably predict the association constants of adducts for which experimental data are not available yet. [ABSTRACT FROM AUTHOR]

In this paper, we report the synthesis and biological evaluation of picolylamide-based diselenides with the aim of developing a new series of diselenides with O•••Se non-bonded interactions. The synthesis of diselenides was performed by a simple and efficient synthetic route. All the products were obtained in good yields and their structures were determined by 1H-NMR, 13C-NMR and HRMS. All these new compounds showed promising activities when tested in different antioxidant assays. These amides exhibited strong thiol peroxidase-like (TPx) activity. In fact one of the compounds showed 4.66 times higher potential than the classical standard i.e., diphenyl diselenide. The same compound significantly inhibited iron (Fe)-induced thiobarbituric acid reactive species (TBARS) production in rat's brain homogenate. In addition, the X-ray structure of the most active compound showed non-bonded interaction between the selenium and the oxygen atom that are in close proximity and may be responsible for the increased antioxidant activity. The present study provides evidence about the possible biochemical influence of nonbonding interactions on organochalcogens potency. [ABSTRACT FROM AUTHOR]

From a pharmacological point of view, organoseleniums are compounds with important and interesting antioxidant and biological activities. The aim of this study was to evaluate the hepatoprotective effect of bis(4-methylbenzoyl) diselenide (BMD) against carbon tetrachloride (CCl4)-induced oxidative damage in mice. The animals received BMD (25 mg/kg p.o., for 3 days), and after 1 day, CCl4 (1 mg/kg body weight) was administered by intraperitoneal route. One day after the CCl4 exposure, the animals were euthanized for biochemical and histological analysis. Treatment with BMD (25 mg/kg p.o.) protected against aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase and lactate dehydrogenase activity increases induced by CCl4 plasma exposure. Treatment with BMD (25 mg/kg) protected against increases in thiobarbituric reactive species and decreasing non-protein thiols and ascorbic acid levels in liver of mice. Catalase and superoxide dismutase activity inhibition in the liver caused by CCl4 were protected by treatment with BMD (25 mg/kg). Glutathione S-transferase activity was inhibited by CCl4 and remained unaltered even after treatment with BMD. Sections of liver from CCl4-exposed mice presented an intense infiltration of inflammatory cells and loss of the cellular architecture. BMD (25 mg/kg) attenuated CCl4-induced hepatic histological alterations. The results demonstrated the hepatoprotective effects of BMD in the mouse liver, possibly by modulating the antioxidant status. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Herein, we report an eco-friendly synthesis of selenoesters from acyl chlorides catalyzed by recyclable CuO nanopowder in ionic liquid as a recyclable solvent in good to excellent yields. This protocol shows high efficiency in catalyzing this transformation in a greener fashion than previous protocols due to the non-residual methodological design. [ABSTRACT FROM AUTHOR]

Schiff bases represent a valuable class of organic compounds, synthesized via condensation of primary amines with ketones or aldehydes. They are renowned for possessing innumerable applications in agricultural chemistry, organic synthesis, chemical and biological sensing, coating, polymer and resin industries, catalysis, coordination chemistry, and drug designing. Schiff bases contain imine or azomethine (-C=N-) functional groups which are important pharmacophores for the design and synthesis of lead bioactive compounds. In medicinal chemistry, Schiff bases have attracted immense attention due to their diverse biological activities. This review aims to encompass the recent developments on the antimicrobial activities of Schiff bases. The article summarizes the antibacterial, antifungal, antiviral, antimalarial, and antileishmanial activities of Schiff bases reported since 2011., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The present study investigated the antidepressant-like potential of a functionalized 3-selanyl benzo[ b ]furan (SeBZF) in male Swiss mice. To evaluate possible antidepressant-like actions, the compounds SeBZF 1-5 (50 mg/kg, intragastric, i.g., route) were acutely screened in the tail suspension tests (TSTs). The compound 3-((4-methoxyphenyl)selanyl)-2-phenylbenzofuran (SeBZF 3 ) was then selected. Dose-response and time-response curves revealed that SeBFZ 3 exerts antidepressant-like effects in the TST (5-50 mg/kg) and forced swimming test (FST; 50 mg/kg). Additional tests demonstrated that pretreatment with receptor antagonists WAY100635 (5-HT 1A ; 0.1 mg/kg, subcutaneous route), ketanserin (5-HT 2A/C ; 1 mg/kg, intraperitoneal, i.p.), or ondansetron (5-HT 3 ; 1 mg/kg, i.p.) blocked the SeBZF 3 antidepressant-like effects (50 mg/kg) in the TST. In addition, the coadministration of subeffective doses of SeBZF 3 (1 mg/kg, i.g.) and fluoxetine (a selective serotonin reuptake inhibitor; 5 mg/kg, i.p.) produced synergistic action. A high dose of SeBZF 3 (300 mg/kg) did not produce oral acute toxicity. The present results provide evidence for the antidepressant-like action of SeBZF 3 and its relative safety, as well as predict the possible interactions with the serotonergic system, aiding in the development of novel options to alleviate psychiatric disabilities.

Background: COVID-19 is still causing long-term health consequences, mass deaths, and collapsing healthcare systems around the world. There are no efficient drugs for its treatment. However, previous studies revealed that SARS-CoV-2 and SARS-CoV have 96% and 86.5% similarities in cysteine proteases (3CL pro ) and papain-like protease (PL pro ) sequences, respectively. This resemblance could be important in the search for drug candidates with antiviral effects against SARS-CoV-2., Objective: This paper is a compilation of natural products that inhibit SARS-CoV 3CL pro and PL pro and, concomitantly, reduce inflammation and/or modulate the immune system as a perspective strategy for COVID-19 drug discovery. It also presents in silico studies performed on these selected natural products using SARS-CoV-2 3CL pro and PL pro as targets to propose a list of hit compounds., Methods: The plant metabolites were selected in the literature based on their biological activities on SARS-CoV proteins, inflammatory mediators, and immune response. The consensus docking analysis was performed using four different packages., Results: Seventy-nine compounds reported in the literature with inhibitory effects on SARS-CoV proteins were reported as anti-inflammatory agents. Fourteen of them showed immunomodulatory effects in previous studies. Five and six of these compounds showed significant in silico consensus as drug candidates that can inhibit PL pro and 3CL pro , respectively. Our findings corroborated recent results reported on anti-SARS-CoV-2 in the literature., Conclusion: This study revealed that amentoflavone, rubranoside B, savinin, psoralidin, hirsutenone, and papyriflavonol A are good drug candidates for the search of antibiotics against COVID-19., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)