Alessandro Contini

• PhD
• Professor (Associate) at University of Milan

A refresh and improvement of the well‐known myo‐inositol chemistry is reported here, setting up a new synthetic protocol to obtain orthogonally protected compounds, with a special focus on the preparation of 2‐O‐alkylated compounds. A gram scale synthesis of the 2‐allyl compound was performed and optimized in terms of yield. This intermediate is th...

The coupling between bis(2-oxazolines) and two equivalents of aromatic aldehydes in the presence of catalytic amounts of NiCl2 affords an ester-imine product in synthetically useful yields. This virtually unknown, 100% atom-economic transformation involves the formal metathesis between the C=N double bond of the bis(2-oxazoline) moiety, which under...

We report the results of the COVID Moonshot, a fully open-science, crowdsourced, and structure-enabled drug discovery campaign targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease. We discovered a noncovalent, nonpeptidic inhibitor scaffold with lead-like properties that is differentiated from current main protea...

Mycobacterium tuberculosis ( M.tb ), the causative agent of Tuberculosis, threats human lives more than any other infectious diseases worldwide. Despite of various developed drugs against M.tb , lack of an efficient therapeutic has led to continuous formulation of new drugs against the disease. The bacteria's specific adaptations to achieve drug re...

A phosphine-catalyzed domino assembly of six units of 2-bromomethyl acrylates afforded polyalkenyl adducts containing two cyclohexenyl rings. This reaction occurs under mild conditions providing the final product by formation of seven carbon–carbon bonds and four stereocenters. Experimental and computational studies support an initial dimerization...

Many studies have demonstrated how the pyrrolidine nucleus is more efficient than the corresponding piperidine or morpholine as organocatalysts in the condensation of aldehydes with electrophiles via enamine. Focussing on morpholine–enamines, their low reactivity is ascribed to the presence of oxygen on the ring and to the pronounced pyramidalisati...

Though the bulk of the COVID-19 pandemic is behind, the search for effective and safe anti-SARS-CoV-2 drugs continues to be relevant. A highly pursued approach for antiviral drug development involves targeting the viral spike (S) protein of SARS-CoV-2 to prevent its attachment to the cellular receptor ACE2. Here, we exploited the core structure of...

Accelerated molecular dynamics (aMD) protocols were assessed on predicting the secondary structure of eight peptides, of which two are helical, three are β-hairpins, and three are disordered. Protocols consisted of combinations of three force fields (ff99SB, ff14SB, ff19SB) and two explicit solvation models (TIP3P and OPC), and were evaluated in tw...

The design and synthesis of a series of peptide derivatives based on a short ACE2 α-helix 1 epitope and subsequent [i - i+4] stapling of the secondary structure resulted in the identification of a 9-mer peptide capable to compete with recombinant ACE2 towards Spike RBD in the micromolar range. Specifically, SARS-CoV-2 Spike inhibitor screening base...

Structures composed of alternating α and β amino acids can give rise to peculiar secondary structural motifs, which could self-assemble into complex structures of controlled geometries. This work describes the self-assembly properties of an α,β-peptide, containing three units of syn H2-(2-F-Phe)-h-PheGly-OH, able to self-organize on surfaces into a...

SARS-CoV-2 is a highly contagious virus that has caused serious health crisis, resulting into a global pandemic situation. Widespread vaccination and current clinical management have strongly reduced both mortality and severity of COVID-19, but serious concerns still remain, including resistance mechanisms to vaccines, difficulties in effective pro...

New peptidomimetics containing a β2,2‐isoxazoline amino acid, 5‐(aminomethyl)‐3‐phenyl‐4,5‐dihydroisoxazole‐5‐carboxylic acid (Isox‐β2,2AA), were prepared and studied by NMR and theoretical calculations. Interestingly, inserting R‐Isox‐β2,2AA in short tri‐ and hexapeptide models, an unexpected α‐turn‐like motif was observed, thanks to an unpreceden...

Paroxetine is a widely used antidepressant drug, usually prescribed to treat major depression disorder, anxiety, but is also common in managing chronic pain, eating disorders, some forms of headache and sleep disturbances. Antidepressants, and paroxetine in particular, are linked to side effects, and sexual dysfunction is one of the most prevalent....

Asparagine endopeptidase (AEP), also called legumain, is a pH-dependent endolysosomal cysteine protease that cleaves its substrates after asparagine residues. Recent studies showed that it possesses δ-secretase activity and that it is implicated in numerous neurological diseases such as Alzheimer’s disease (AD). Following evidence of aryl-morpholin...

Malaria accounts for millions of cases and thousands of deaths every year. In the absence of an effective vaccine, drugs are still the most important tool in the fight against the disease. Plasmodium parasites developed resistance for all the classes of known antimalarial drugs. Thus, the search for antimalarial drugs with novel mechanisms of actio...

In our previous study, we had identified a 9-mer peptide (FSHβ (89-97)) derived from seat belt loop of human FSHβ and demonstrated its ability to function as FSHR antagonist in vivo. Structure analysis revealed that the four central residues ⁹¹STDC⁹⁴ within this peptide may not be critical for receptor binding. In the present study, ⁹¹STDC⁹⁴ residu...

Finasteride, a 5-alpha reductase (5α-R) inhibitor, is a widely used drug for treating androgen-dependent conditions. However, its use is associated with sexual, psychological, and physical complaints, suggesting that other mechanisms, in addition to 5α-R inhibition, may be involved. Here, a multidisciplinary approach has been used to identify poten...

The chemical structure of oligonucleotide analogues dictates the conformation of oligonucleotide analogue oligomers, their ability to hybridize complementary DNA and RNA, their stability to degradation and their pharmacokinetic properties. In a study aimed at investigating new analogues featuring a neutral backbone, we explored the ability of oligo...

A useful aminohalogenation reaction for the cyclization of O‐alkynyl carbamates under copper catalysis has been developed. N‐Halosuccinimides have been used as a halogen source. The intramolecular C−N bond formation occurs selectively affording haloalkylidene substituted heterocycles. Just in the case of α,α‐cyclohexyl‐substituted propargyl carbama...

The lack of accurate and easily applicable methods for the diagnosis of liver fibrosis, a disease characterized by an accumulation of extracellular matrix released by activated hepatic stellate cells (HSCs), has been a major limitation for the clinical management of liver diseases. The identification of biomarkers specific to liver microstructure a...

Herein we provide a living summary of the data generated during the COVID Moonshot project focused on the development of SARS-CoV-2 main protease (Mpro) inhibitors. Our approach uniquely combines crowdsourced medicinal chemistry insights with high throughput crystallography, exascale computational chemistry infrastructure for simulations, and machi...

The pandemic caused by SARS-CoV-2 is currently representing a major health and economic threat to humanity. So far, no specific treatment to this viral infection has been developed and the emergency still requires an efficient intervention. In this work, we used virtual screening to facilitate drug repurposing against SARS-CoV-2, targeting viral ma...

One of the strategies of peptide–protein docking is to pregenerate an ensemble of peptide conformations in the absence of the receptor, and then dock them as rigid bodies onto its surface. Success of this strategy requires that the scoring function that drives the pregeneration step be able to discriminate in favor of conformations that resemble th...

Despite a high degree of structural similarity, it is known that MMP2 and MMP9 have distinct roles in the angiogenic switch and in cell migration, as they activate diverse signaling pathways. Indeed, inhibition of MMP2 and MMP9 can show beneficial or detrimental effects depending on the stage of tumor progression. Thus, the selective inhibition of...

A new non-natural β-amino acid, named 3-Ar-β-Morph, was designed and synthesized via a regio- and diastereoselective Pd-catalyzed C(sp3)H-arylation of the corresponding 2S,6S-(6-methoxymorpholin-2-yl)carboxylic acid, readily available from glucose. According to the computational prevision and confirmed by IR and NMR data, the insertion of 3-Ar-β-Mo...

FSH-FSHR interaction is critical for folliculogenesis, spermatogenesis and progression of several cancers. Therefore, FSHR is an attractive target for fertility regulation and cancer therapeutics. Based on homology and structural analysis of hFSH-FSHR(ECD) complex, a minimal continuous stretch within FSHβ seat-belt loop (FSHβ (89-97)) was identifie...

A stereodivergent strategy to obtain enantiopure cis and trans 4‐aminopipecolic acids (4‐APAs) in a suitably protected form for peptide synthesis has been devised starting from a common, known precursor in turn easily prepared from commercial (R)‐4‐cyano‐3‐hydroxybutyric acid ethyl ester. The two isomers were efficiently obtained in 40 % and 23 % o...

div>The infection by the 2019-nCoV coronavirus (COVID-19) is a world-wide emergency. The crystal structure of a protein essential for virus replication has been filed in the Protein Data Bank recently. Additionally, homology models of 24 COVID-19 proteins were made available by the Zhang group. In this paper, we present results deriving from the...

div>The infection by the 2019-nCoV coronavirus (COVID-19) is a world-wide emergency. The crystal structure of a protein essential for virus replication has been filed in the Protein Data Bank recently. Additionally, homology models of 24 COVID-19 proteins were made available by the Zhang group. In this paper, we present results deriving from the...

The human inducible phospho-fructokinase bisphosphatase isoform 3, PFKFB3, is a crucial regulatory node in the cellular metabolism. The enzyme is an important modulator regulating the intracellular fructose-2,6-bisphosphate level. PFKFB3 is a bifunctional enzyme with an exceptionally high kinase to phosphatase ratio around 740:1. Its kinase activit...

With the potential of improving virtual screening outcome, MM-PB/GBSA has become a disputed method that requires extensive testing and tuning to provide the optimal results. One of the tuning factors is the internal or solute dielectric constant. We have applied three test sets with receptors of different categories and libraries from different sou...

MMP2 and MMP9, also called gelatinases, play a primary role in the angiogenic switch, as a fundamental step of tumor progression, and show high degree of structural similarity. Clinically successful gelatinase inhibitors need to be highly selective as opposite effects have been found for the two enzymes, and the S1' subsite is the major driver to a...

α,β2,3-Disteroisomeric foldamers of general formula Boc(S-Ala-β-2R,3R-Fpg)nOMe or Boc(S-Ala-β-2S,3S-Fpg)nOMe were prepared from both enantiomers of syn H-2-(2-F-Phe)-h-PheGly-OH (named β-Fpg) and S-alanine. Our peptides show two appealing features for biomedical applications: the presence of fluorine, attractive for non-covalent interactions, and a...

Background: The activation of follicle stimulating hormone receptor (FSHR) by FSH and the consequent downstream signaling activities are crucial for reproductive health. The role of FSHR in tumor progression as well as osteoporosis advancement has also been well established. Currently, steroid preparations of estrogen and progesterone are being us...

A new cyclic enantiopure β-amino acid, named β-Morph, containing the morpholino ring, was obtained in gram scale starting from α-D-glucopyranose enantiopure material, focusing on the “environmental sustainability” concept. A series of ultrashort model peptides containing β-Morph were prepared. β-Morph was found able to induce an inverse γ-turn in L...

Phospine free hydroarylation reaction applied to norbornene derivatives is described for the first time and was exploited for the regioselective gram scale synthesis of AR-148 a known Rac1-Tiam1 PPI inhibitor. Umpolung conversion of nitro group to the free amine allowed the regiocontrol of the key arylation step via long range effect. The effect of...

Tetrahydro-4H-(pyrrolo[3,4-d]isoxazol-3-yl)methanamine scaffold was designed as diamino derivative to stabilize parallel turn conformations. Its synthesis took advantage of a [1,3]-dipolar cycloaddition reaction between the nitrile oxide derived from the inexpensive enantiopure L-phenylalanine, and N-benzyl-3-pyrroline. Two diastereoisomers were fo...

Background: The inclusion of direct effects mediated by water during the ligand-receptor recognition is a hot-topic of modern computational chemistry applied to drug discovery and development. Docking or virtual screening with explicit hydration is still debatable, despite the successful cases that have been presented in the last years. Indeed, ho...

A stereodivergent strategy was devised to obtain enantiopure cis and trans 5-aminopipecolic acids (5-APAs) in suitably protected forms to be employed in peptide synthesis as conformationally constrained α- and δ-amino acids. The cis isomer was used as a δ-amino acid to construct a cyclic RGD-containing peptidomimetic, the ability of which to compet...

Nwat-MMGBSA is a variant of MM-PB/GBSA based on the inclusion of a number of explicit water molecules that are the closest to the ligand in each frame of a molecular dynamics trajectory. This method demonstrated improved correlations between calculated and experimental binding energies in both protein-protein interactions and ligand-receptor comple...

Rac1 GTPase interaction with guanine nucleotide exchange factor Tiam1 is involved in several cancer types and cardiovascular diseases. Although small molecules interfering with their protein-protein interaction (PPI) were identified and studied, the ability of small peptides and peptide mimics acting as Rac1/Tiam1 PPI inhibitors has not been yet ex...

This work reports a joint experimental-theoretical investigation of pyrrolyl-silicon compounds with different alkyl spacers, namely propyl, butyl and hexyl side chains carrying silicon-based end groups. For the electrochemical study, the monomers with methoxysilyl end groups spaced through butyl and hexyl chains were ad-hoc synthesized. Structurall...

In the present study the esterification of the hydroxyl groups of resveratrol, caffeic acid, ferulic acid and ß-sitosterol with an antioxidant polyconjugated fatty acid, 2E,4E,6E-octatrienoic acid, was achieved. As the selective esterification of hydroxyl groups of natural compounds can affect their biological activity, a selective esterification o...

The conformational analysis of linear and cyclic peptides incorporating 2,3-methanopipecolic acids (or Cyclopropane Pipecolic Acids, CPAs) as conformationally constrained α-amino acids is reported. Compared to peptides containing proline or pipecolic acid, a striking increase of the cis isomer (42-92%) around the CPA amide bond is observed, both in...

Tetrahydroisoquinoline-4-carboxylic acid, a constrained β2-amino acid named β-TIC, was for the first time synthesized in enantiopure form. The biocatalytic route here applied represents one of the few successful examples of enzymatic resolution of β2-amino acids. Model tetrapeptides, i.e. Fmoc-L-Ala-β-TIC-β-Ala-L-Val-OBn, containing both isomers of...

Helical oligomers of achiral monomers adopt domains of uniform screw sense which are occasionally interrupted by screw-sense reversals. These rare, elusive, and fast-moving features that have eluded detailed characterization. We now describe the structure and habits of a screw-sense reversal trapped within a fragment of helical oligoamide foldamer...

The Nwat-MMGBSA method, whose theory has been described in Maffucci & Contini, JCTC 2013, 9, 2706, is based on the inclusion as part of the receptor of a given number of water molecules (Nwat) which are the closest to a residue (generally the ligand) or to a selection of residues (the contact interface) in each frame of the MD simulation. The metho...

Alzheimer’s disease is a neurodegenerative disorder linked to oligomerization and fibrillization of amyloid β peptides, with Aβ1-42 being the most aggregative and neurotoxic one. We report herein the synthesis and conformational analysis of Aβ1-42 -amyloid related β-hairpin peptidomimetics, built on a piperidine-pyrrolidine semi rigid β-turn induce...

The synthesis of a new hexacyclic system was realized starting from tryptamines and exploiting as a key step a sequential Pd-catalyzed N-arylation/acylation reaction. Having topoisomerases as biological target and the campthotecins class as benchmark, the new scaffold was decorated with substituents having different polarity and tested as Topoisome...

A MMGBSA variant (here referred to as Nwat-MMGBSA), based on the inclusion of a certain number of explicit water molecules (Nwat) during the calculations, has been tested on a set of 20 protein-protein complexes, using the correlation between predicted and experimental binding energy as the evaluation metric. Beside the Nwat parameter, the effect o...

Atropisomeric biaryl pyridine and isoquinoline N-oxides were synthesized enantioselectively by dynamic kinetic resolution (DKR) of rapidly racemizing precursors exhibiting free bond rotation. The DKR was achieved by ketoreductase (KRED) catalyzed reduction of an aldehyde to form a configurationally stable atropisomeric alcohol, with the substantial...

Atropisomeric biaryl pyridine and isoquinoline N-oxides were synthesized enantioselectively by dynamic kinetic resolution (DKR) of rapidly racemizing precursors exhibiting free bond rotation. The DKR was achieved by ketoreductase (KRED) catalyzed reduction of an aldehyde to form a configurationally stable atropisomeric alcohol, with the substantial...

Taking inspiration from the Ctr-1 Mets7 Cu(I) binding motif, effective hybrid catalysts have been developed for asymmetric Henry condensations under green conditions. The introduction of an unnatural dipeptide mimic allowed to increase the catalytic performance. Metal transporters' binding domains could be exploited as a strategy for designing hybr...

The possibility of obtaining an efficient artificial imine reductase was investigated by introducing a chiral cofactor into artificial metalloenzymes based on biotin-streptavidin technology. In particular, a chiral biotinylated 1,3-diamine ligand in coordination with iridium(III) complex was developed. Optimized chemogenetic studies afforded positi...

Replica Exchange Molecular Dynamics simulations were performed to test the ability of six AMBER force fields and three implicit solvent models of predicting the native conformation of two helical peptides, three β-hairpins and three intrinsically disordered peptides. Although a combination of force field and implicit solvation model able to accurat...

The mechanisms behind the propensity of chiral constrained Cα-tetrasubstituted amino acids (cCTAAs) to induce one particular helical screw sense, when included in the Ac-Aib2-cCTAA-Aib2-NHMe peptide model, were studied through replica exchange molecular dynamics, potential of mean force and quantum theory of atoms in molecules calculations. We obse...

Vibrational circular dichroism, VCD, gives evidence that the carbon monoxide chromophore in a heteroleptic cyclopentadienyl Ru(ii)-carbonyl complex is very sensitive to the chirality of the metal centre and becomes an excellent probe to define the configuration of chiral metal complexes.

A new alpha,alpha-disubstituted constrained glutamine analogue was designed to decorate gold-nanoparticles and to induce 310-helix when inserted in peptides. Using an efficient "one-pot" asymmetric Schmidt reaction, between 4-disubstituted-cyclohexanone and hydroxyalkylazides, 1H-azepine-2-oxo-5-amino-5-carboxylic acid, (oxo-Azn) was prepared. The...

The properties of the constrained tetrasubstituted 3-sulfanylnorbornene amino acid (NRB), when inserted in Ala-Aib model peptides, were extensively studied. The conformational behaviour of these models was evaluated by theoretical calculations, spectroscopic analyses and by X-ray crystallography. Taken together, our data confirm that both (R,R,R,S)...

Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) and Molecular Mechanics Generalized Born Surface Area (MM-GBSA) are widely used methods for the prediction of binding free energies in drug design/discovery. Indeed, their computational efficiency makes them applicable also within virtual screening protocols. Thus, in order to be useful f...

The theoretical basis behind the ability of constrained Cα-tetrasubstituted amino acids (CTAAs) to induce stable helical conformations has been studied through Replica Exchange Molecular Dynamics, Potential of Mean Force and Quantum Theory of Atoms In Molecules calculations on Ac-L-Ala-CTAA-L-Ala-Aib-L-Ala-NHMe peptide models. We found that the ori...

The Maf protein family belongs to the activator protein 1 (AP-1) superfamily of transcription factors that bind specific DNA target sequences through a basic region and exploit a leucine zipper (LZ) motif for protein-protein interactions leading to homo- or hetero-dimerization. Mafs unique DNA-binding domain contains a highly conserved extended hom...

A new semi-rigid dipeptide mimetic was prepared in multigram scale, in good yield and in a stereocontrolled way, starting from commercially available and unexpensive reagents, i. e. N-benzyl piperidone, tosyl azide and proline methyl ester. The optimized multicomponent process consisted of a cascade click cycloaddition and a ring rearrangement reac...

The use of the 2-amino-3-(phenylsulfanyl)norbornane-2-carboxylate scaffold has been exploited for the de-novo design of potent Rac1 inhibitors acting as modulators of the protein-protein interaction between Rac1 and Tiam1. A series of compounds, differing in regio- and stereochemistry has been prepared by way of a multistep synthesis based on cyclo...

Quercetin shows interesting pharmacological effects, but its use in topical applications is limited by its low skin permeability and solubility. In this work, the synthesis of highly lipophilic quercetin esters with oleic, linoleic and linolenic acid useful as topical quercetin prodrugs is reported. Partial OH esterification is advisable to maintai...

Herein is reported the authors' experiences in establishing the Scientists Against Malaria (SAM) initiative, and the strategies employed, collaboration approach and supporting infrastructure are discussed. The collaboration initially progressed kinase inhibitor design and testing against a Plasmodium falciparum kinase as an antimalarial drug target...

A pathway-based genome-wide association analysis has recently identified Rac1 as one of the biologically important gene in coronary heart diseases. The role of the small GTPase Rac1 in cardiac hypertrophy and atherosclerosis has also been documented in clinical studies with the HMG-CoA reductase inhibitors, and in in vitro and in vivo settings usin...

Transcriptional dysregulation is a hallmark of Huntington's disease (HD) and one cause of this dysregulation is enhanced activity of the REST‐ mSIN 3a‐ mSIN 3b‐CoREST‐HDAC repressor complex, which silences transcription through REST binding to the RE1/NRSE silencer. Normally, huntingtin (HTT) prevents this binding, allowing expressing of REST targe...

Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) and Molecular Mechanics Generalized Born Surface Area (MM-GBSA) methods are widely used for drug design/discovery purposes. However, it is not clear if the correlation between predicted and experimental binding affinities can be improved by explicitly considering selected water molecules...

We describe the application of molecular dynamics followed by principal component analysis to study the inter-domain movements of the ligand binding domain (LBD) of mGluR5 in response to the binding of selected agonists or antagonists. Our results suggest that the method is an attractive alternative to current approaches to predict the agonist-indu...

Through a computational approach, five new compounds with potent and selective Rac inhibitory activity were identified. In particular, compound 4 was shown to selectively inhibit Rac activity in a concentration-dependent manner by affecting the GEF-dependent GDP–GTP exchange. This compound was more potent than the original inhibitors previously ide...

The effects on tubulin dynamics of paclitaxel, ortataxel and two recently developed taxol derivatives bearing a five-membered heterocyclic ring fused at the 1,14 position were analysed by means of molecular dynamic simulations and the MM-PBSA approach. Tubulin polymerization kinetics and microtubule morphology assays were also conducted, providing...

The cycloaddition reaction of the morpholino enamines of N-methylpiperidone and N-methyl tropinone with sulfonylazides was exploited, leading to a click-chemistry approach to uncommon azacycloalkene monosulfonyl diamines in good yields. A computational model for the key step decomposition of the triazoline intermediate was then realized by DFT calc...

Novel 6-aryl-2-methylnicotinic acid hydrazides 4a-c and their corresponding hydrazones 5a-c and 6a-i were synthesized. X-ray single crystal diffraction of 6h confirmed the chemical structure of hydrazones 6a-i. Antiproliferative activity of the synthetic compounds was investigated against K562 leukemia cell lines. Variable cell growth inhibitory ac...

A very efficient synthesis of orthogonally protected 1H-azepine-4-amino-4-carboxylic acid, abbreviated as Azn, a conformationally restricted analogue of ornithine, was realized. It was obtained on a gram scale in good overall yield in five steps, three of which did not require isolation of the intermediates, starting from the readily available 1-am...

A series of pentyl-sulfonyl amidines was obtained using a multicomponent synthesis process. The rearrangement of unstable tosylazide-cyclopentanonenamine cycloadducts yielded a diazoalkane intermediate. This primary, unstable reaction product showed good reactivity with certain acid compounds in order to form the corresponding derivatives.

An expedient chemical synthesis of a 75mer peptide corresponding to the DNA binding domain (DBD, 227-301) of the human MafA leucine zipper transcription factor is reported. The application of microwave-assisted solid phase peptide synthesis (MW-SPPS) with a protocol modified respect to the standard one allowed obtaining the desired 75mer peptide in...

Scientists Against Malaria (SAM) is an international virtual organization designed to apply modern drug design and modeling techniques in combination with industry std. infrastructure and interdisciplinary science to develop new treatments against malaria. Our strategy strongly relies on the use and development of a novel collaborative research wor...

Organocatalysts able to catalyze Diels-Alder cycloaddn. reactions of α,β-unsatd. aldehydes were studied from both synthetic and theor. perspectives. The importance of the imidazolidinone scaffold and the influence of the functional groups upon the formation of the reactive species was evaluated. Also taking into account that all these new organoc...

Bis-2,3-heteroarylmaleimides and polyheterocondensed imides joined through nitrogen atoms of the N,N'-bis(ethyl)-1,3-propanediamine linker were prepared from substituted maleic anhydrides and symmetrical diamines in good to satisfactory yields and short reaction times using microwave heating. The novel molecules were shown to inhibit proliferation...

A very efficient three-component synthesis of a series of syn α-hydroxy-β-amino esters, obtained in high diastereoselection and yield, was realized starting from an aldehyde, benzylamine, and the ketene silyl acetals derived from Ley's lactones. The synthetic protocol was optimized and the above compounds were obtained without the isolation of inte...

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The reaction of benzenesulfenic acid, generated in situ by thermal decompn. of 3-(phenylsulfinyl)propanenitrile, with monosubstituted acetylenes was exptl. and theor. studied at the DFT level using the MPW1B95 d. functional. A computational model based on the Hard Soft Acid Base (HSAB) principle was evaluated for its ability to qual. and quant. pre...

Herein we report a mild and efficient method to synthesize chiral 3-aminosubstituted isothiazole sulfoxides taking advantage of (+)- and (−)-((8,8-dichlorocamphoryl)sulfonyl)oxaziridine under microwave irradiation. The determination of the absolute configuration of the chiral sulfoxide was achieved by theoretical calculation of the CD spectra. The...

REST/NRSF is a transcription factor that represses transcription of several neuronal genes by binding to a DNA regulatory motif known as Repressor Element 1/Neuron-restrictive silencer element (RE1/NRSE). In Huntington's Disease, an inherited degenerative disease affecting the brain, REST/NRSF enters pathologically into the nucleus of affected cell...

Rac1 protein is implicated in several events of atherosclerotic plaque development and represents a new potential pharmacological target for cardiovascular diseases. In this paper we describe a pharmacophore virtual screening followed by molecular docking calculations leading to the identification of five new Rac1 inhibitors. These compounds were s...

The cycloaddition reactions of ‘all-carbon’ 1,3-diazabuta-1,3-dienes with a few conjugated and unconjugated alkynyl ketenes are described. The reactions provide some interesting azetidinones and dihydropyrimidinones bearing an alkynyl moiety. The regiochemistry of cycloadduct is related with the degree of conjugation of the alkynyl ketene. Moreover...

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.