Diversity-oriented synthesis and antibiofilm evaluation of furan-2-carboxamides.

A diversity-oriented collection of furan-2-carboxamides with antibiofilm activity against P. aeruginosa is reported. The design involved the bioisosteric replacement of the labile furanone ring by a furan-2-carboxamide moiety to explore its influence on biological activity.

Identification of Potential Inhibitors of Amidases: An Integrated In Silico and Experimental Study.

Virtual screening is a crucial tool in early stage drug discovery for identifying potential hit candidates. Here, we present an integrated approach that combines theoretical and experimental techniques to identify, for the first time, inhibitors of amidases (Ami1-Ami4) from . Through computational methods, we proposed a set of potential inhibitors, which were subsequently evaluated experimentally using differential scanning fluorimetry.

N-acyl-4-arylaminopiperidines: Design and synthesis of a potential antimicrobial scaffold.

We report a concise synthesis of N-acylated piperidines through a Knoevenagel-Doebner condensation/amide construction/ amination sequence. The design of the piperidines considered the pharmacophoric features found in previously reported inhibitors of FabI, an enzyme implicated in bacterial fatty acid biosynthesis. After the microbiological evaluation at 50 μM, the analogs displayed moderate activity against some pathogens from the ESKAPE group, reaching up to 42 % of growth inhibition for MRSA, 54 % for K.

Discovery of dual-action phenolic 4-arylidene-isoquinolinones with antioxidant and α-glucosidase inhibition activities.

A multicomponent-derived synthesis of arylidene isoquinolinones decorated with phenolic moieties is described. The series demonstrated good DPPH trapping and, in the case of sinapic acid-containing analogs, excellent activity against lipoperoxidation; EPR also demonstrated that one derivative scavenged hydroxyl radicals. In addition, some compounds showed excellent inhibition of α-glucosidase activity and, according to both Lineweaver-Burk plots and molecular docking, they act as non-competitive or mixed inhibitors.

Synthesis, antibiofilm activity and molecular docking of N-acylhomoserine lactones containing cinammic moieties.

We prepared a series of cinnamoyl-containing furanones by an affordable and short synthesis. The nineteen compounds hold a variety of substituents including electron-donating, electron-withdrawing, bulky and meta-substituted phenyls, as well as heterocyclic rings. Compounds showed antibiofilm activity in S.

A regioselective synthesis of 3,4-diaryl-1-pyrazoles through a 1,3-dipolar cycloaddition of tosylhydrazones and nitroalkenes.

A procedure for the selective synthesis of 3,4-diaryl-1-pyrazoles through a 1,3-dipolar cycloaddition is reported. The transformation occurred under mild conditions using affordable tosylhydrazones and nitroalkenes commencing from benzaldehydes/heteroaromatic aldehydes as starting materials. Due to the versatility of this protocol, we prepared a vast collection of 3,4-diaryl-1-pyrazoles, which included the incorporation of heterocyclic rings at the pyrazole core.

First-principles study of Mn adsorbed on Au(111) and Cu(111) surfaces.

A theoretical study of the Mn trimer adsorbed on the noble metal surfaces Au(111) and Cu(111) is reported. The calculations were performed using first-principles methods within the density functional theory and the generalized gradient approximation in the collinear and non-collinear magnetic phases. The system was modeled by considering a surface unit cell of 25 atoms to improve the trimer's isolation on the surface.

Expanding the structure-activity relationship of cytotoxic diphenyl macrocycles.

Twenty-four biaryl tetrapeptide macrocycles were synthesized as an extension of our previous work. Two groups of compounds were constructed for establishing a structure-activity relationship: one having an aromatic substituent at α-position of one exo-peptide and the other group with a variation in the size of the lipophilic chain. Compound 13t had the best cytotoxicity from all the compounds tested (in a panel of six human cancer cell lines) and low toxicity on one healthy cell line.

Discovery of Benzopyrrolizidines as Promising Antigiardiasic Agents.

Current treatments for giardiasis include drugs with undesirable side effects, which increase the levels of therapeutic desertion and promote drug resistance in the parasites. Herein, we describe the antigiardiasic evaluation on Giardia lamblia trophozoites of a structurally diverse collection of 74 molecules. Among these scaffolds, we discovered a benzopyrrolizidine derivative with higher antigiardiasic activity (IC = 11 µM) and lower cytotoxicity in human cell cultures (IC = 130 µM) than those displayed by the current gold-standard drugs (metronidazole and tinidazole).

Multicomponent synthesis and anti-proliferative screening of biaryl triazole-containing cyclophanes.

We report a practical two-step approach involving a Ugi 4-CR/ azide-alkyne cycloaddition for the synthesis of biaryl-containing cyclophanes. The series represents an extension of our previously reported macrocycles as an effort to enhance the anti-proliferative activity of this scaffold. In this variant, we incorporate a biphenyl moiety in the framework, thus enhancing the macrocycle size, lipophilicity, and structural diversity.

Multicomponent synthesis and preliminary anti-inflammatory activity of lipophilic diphenylamines.

Non-Steroidal Anti-inflammatory Drugs (NSAIDs) are some of the most prescribed medications for pain but the incidence of adverse effects -especially during chronic treatment- points out the requirement of new analgesics. In this study, we showed an efficient two-steps synthesis of diphenylamine-containing dipeptides consisting of a multicomponent process followed by a Buchwald-Hartwig cross-coupling reaction. We prepared 16 diphenylamine derivatives and evaluated their in vivo anti-inflammatory activity through an ear edema model using 12-O-tetradecanoylpholbol-13-acetate.

First-principles study of Ni adatom migration on graphene with vacancies.

A theoretical study based on first-principles calculations about the interaction and diffusion of Ni atoms on pristine graphene and graphene with a single vacancy is presented. In the first case, we explored the structural changes due to the adsorption of Ni on graphene and the effects on the electronic structure. In the case of graphene with a vacancy, we analyzed the impact of the adsorbed Ni atom on the distortion of the graphene structure and how it depends on the distance from the graphene defect.

Synthesis of diphenylamine macrocycles and their anti-inflammatory effects.

A collection of fourteen diphenylamine macrocyclic derivatives containing a peptide chain with different substituents was synthesized using a protocol of two Ugi four component reactions (Ugi-4CR) and a Buchwald-Hartwig macrocyclization. Their anti-inflammatory effects were assayed with an ear edema model using 12-O-tetradecanoylphorbol-13-acetate, while the activity of myeloperoxidase was determined to evaluate the index of leukocyte infiltration. Compound 5e had an ID50 of 0.

A Two-Step Multicomponent Synthetic Approach and Anti-inflammatory Evaluation of N-Substituted 2-Oxopyrazines.

Inflammation is widely reported as a main factor for the development of chronic diseases such as cancer, diabetes, and even metabolic syndrome. Thus, the search for novel anti-inflammatory compounds is required. Herein we describe the synthesis of a collection of peptidic pyrazinones by a convenient approach involving a multicomponent isocyanide-based reaction followed by a tandem deprotection/oxidative cyclization step.

Acute and subacute antidiabetic studies of ENP-9, a new 1,5-diarylpyrazole derivative.

Objectives: To explore the antihyperglycaemic and antidiabetic effects and to determine the acute toxicity of 5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (ENP-9).

Methods: The antihyperglycaemic effect of ENP-9 (50 mg/kg) was determined by oral glucose tolerance test (OGTT). Also, the acute (16, 50 and 160 mg/kg) and subacute (50 mg/kg/day for 10 days) antidiabetic effects of ENP-9 were determined.

Cytotoxic Activity and Structure-Activity Relationship of Triazole-Containing Bis(Aryl Ether) Macrocycles.

Cancer continues to be a worldwide health problem. Certain macrocyclic molecules have become attractive therapeutic alternatives for this disease because of their efficacy and, frequently, their novel mechanisms of action. Herein, we report the synthesis of a series of 20-, 21-, and 22-membered macrocycles containing triazole and bis(aryl ether) moieties.

Growth of Ni nanoclusters on irradiated graphene: a molecular dynamics study.

We studied the soft landing of Ni atoms on a previously damaged graphene sheet by means of molecular dynamics simulations. We found a monotonic decrease of the cluster frequency as a function of its size, but few big clusters comprise an appreciable fraction of the total number of Ni atoms. The aggregation of Ni atoms is also modeled by means of a simple phenomenological model.

Antidiabetic, antidyslipidemic and toxicity profile of ENV-2: A potent pyrazole derivative against diabetes and related diseases.

Diabetes is a major health problem and a predisposition factor for further degenerative complications and, therefore, novel therapies are urgently needed. Currently, cannabinoid receptor 1 (CB receptor) antagonists have been considered as promissory entities for metabolic disorders treatment. Accordingly, the purpose of this work was the evaluation of the sub-acute antidiabetic, anti-hyperglycemic, antidyslipidemic and toxicological profile of ENV-2, a potent hypoglycemic and antioxidant CB receptor antagonist.

Diversity-oriented synthesis and cytotoxic activity evaluation of biaryl-containing macrocycles.

Synthesis of biaryl-containing macrocycles has been carried out through a four-step approach comprising two Ugi four component reactions and a Suzuki-Miyaura macrocyclization. This protocol allowed the synthesis of 12- and 14-membered macrocycles. Cytotoxic activity evaluation showed that some of the molecules were effective against leukemia, glioblastoma and lung cancer cell lines (IC = 4.

Practical synthesis and cytotoxic evaluation of the pyrazino[1,2-b]-isoquinoline ring system.

A practical three-step protocol for the synthesis of pyrazino[1,2-b]isoquinolines is reported. This approach includes a one-pot parallel cyclization/cyclization parallel process followed by a non-common 6-endo Heck cyclization that transformed previously constructed Ugi adducts into diversely decorated tricyclic systems. Compounds bearing a t-butyl or 2,6-dimethylphenyl substituent showed significant cytotoxic activity.

Synthesis and molecular docking of N'-arylidene-5-(4-chlorophenyl)-1-(3,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carbohydrazides as novel hypoglycemic and antioxidant dual agents.

Herein, the design and synthesis of 10 novel N'-arylidene pyrazole-3-carbohydrazides are described. Compounds were pretended to act as dual agents against diabetes and oxidative stress, two correlated pathologies involved in metabolic syndrome development and progression. The antioxidant capacity was evaluated by means of DPPH and FRAP in vitro assays.

Multicomponent/Palladium-Catalyzed Cascade Entry to Benzopyrrolizidine Derivatives: Synthesis and Antioxidant Evaluation.

A versatile and efficient protocol for the synthesis of highly substituted benzopyrrolizidines (tetrahydro-3H-pyrrolo[2,1-a]isoindol-3-ones) is reported. The strategy consisted of an Ugi four-component reaction/elimination methodology to afford dehydroalanines containing trans-cinnamic acid derivatives and different substituted 2-bromobenzylamines, followed by a palladium-catalyzed 5-exo-trig/5-exo-trig cascade carbocyclization process. Gratifyingly, benzopyrrolizidines were obtained in moderate to good yields (42-77%) with a Z geometry due to the structural requirements for syn-β-hydride elimination.

Ugi-derived dehydroalanines as a pivotal template in the diversity oriented synthesis of aza-polyheterocycles.

Various readily available, Ugi-derived dehydroalanines were used as pivotal templates to easily and efficiently assemble diverse pharmacologically important polyheterocyclic systems through cascade palladium-catalyzed C-C bond formation processes. Allyl, homoallyl and propargylamine led to the formation of benzopyrrolizidinones, benzoindolizidinones and pyrazinoisoquinolines, respectively, while benzylamines and o-bromobenzylamines were used as precursors of tetracyclic-fused systems and pyrazionoisoquinolindiones.

1,5-Diarylpyrazole and vanillin hybrids: Synthesis, biological activity and DFT studies.

Herein, we report the design and synthesis of 13 diarylpyrazole hybrids with vanillin constructed as dual compounds against oxidative stress and diabetes. Compounds were tested in two different antioxidant assays. It was found that all compounds showed an important antioxidant activity in both DPPH and ORAC models and the activity was even more remarkable than vanillin.

ENP11, a potential CB1R antagonist, induces anorexia in rats.

Over the past decade, pharmacological manipulation of cannabinoid 1 receptor (CB1R) has become an interesting approach for the management of food ingestion disorders, among other physiological functions. Searching for new substances with similar desirable effects, but fewer side-effects we have synthesized a SR141716A (a cannabinoid receptor inverse agonist also called Rimonabant) analog, 1-(2,4-Difluorophenyl)-4-methyl-N-(1-piperidinyl)-5-[4-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide, ENP11, that so far, as we have previously shown, has induced changes in glucose availability, i.e.