87 research outputs found
Studio 13-C NMR di oli essenziali di <i>Helicrysum Italicum</i> sub. <i>Microphyllum</i>
In questo lavoro mostriamo l'assegnazione dei componenti maggiori dell'olio essenziale di Elicriso
provenienti da varie zone della Sardegna. Per l'esatta determinazione di alcuni componenti si è resa necessaria una
separazione cromatografica
Structure-based drug design e sintesi di nuovi bioisosteri eterociclici della funzione beta-diketoacida come inibitori dell'enzima HIV-1 integrasi
In questo lavoro, seguendo l’approccio della bioisosteria non classica, la porzione β-diketonica I è stata
incorporata nei nuclei ossazolico III e pirazolico IV e sono stati disegnati gli acidi indolil-3-ossazolici 4ac
e indolil-3-pirazolici 5a-c.
Inoltre la funzione β-diketoacida II, sostituita con un nucleo 3-idrossi-pirrolo-2,5-dionico V, contemplato
in letteratura come bioisostero di tale struttura, ha portato ai derivati 6a-c.
Le molecole progettate sono state sottoposte ad uno studio di docking al fine di di valutare
preliminarmente l’attività inibitoria tramite la costante di inibizione Ki in accordo con il razionale
Structure-based drug design
Strategie di sintesi per la preparazione di bifenili ossidrilati chirali non racemi di interesse agrobiologico
L’attività di ricerca del gruppo è rivolta alla sintesi di bifenili con interessanti caratteristiche
stereochimiche, ottenibili mediante metodi semplici e diretti al fine di un loro utilizzo nei sistemi
biologici ed in agricoltura
Synthesis and study of polyhydroxylated phenol derivatives with potential cosmetic and phytoiatric applications
Tyrosinase (polyphenol oxidase, E.C. 1.14.18.1) and laccase (phenol oxidase, E.C. 1.10.3.2) are multifunctional copper-containing enzymes, that are keys in melanin biosynthesis, melanisation in animals and browning in plants. Our study is aimed to prepare new monomer and dimer phenol derivatives as potential inhibitors of melanin production starting from natural hydroxylated aromatic units
Searching for novel carbonic anhydrase inhibitors: from virtual screening to the lab bench
Carbonic Anhydrases (CAs) are zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide to bicarbonate both in prokaryotes and eukaryotes. In this context, Computer Aided Drug Design strategies have emerged as powerful tools in the modern drug discovery paradigm. In particular, using ligand- and pharmacophore-based virtual screening approaches, we identified novel chemical entities with original chemotypes, that showed an interesting and selective inhibitory activity in nanomolar/low micromolar range toward CA I and CAII, isoforms.
Herein, we present the hit-to-lead optimization process for these prototypes
Natural phenolic inhibitors of trichothecene biosynthesis by the wheat fungal pathogen <i>Fusarium culmorum</i>: a computational insight into the structure-activity relationship
A model of the trichodiene synthase (TRI5) of the wheat fungal pathogen and type-B trichothecene producer Fusarium culmorum was developed based on homology modelling with the crystallized protein of F. sporotrichioides. Eight phenolic molecules, namely ferulic acid 1, apocynin 2, propyl gallate 3, eugenol 4, Me-dehydrozingerone 5, eugenol dimer 6, magnolol 7, and ellagic acid 8, were selected for their ability to inhibit trichothecene production and/or fungal vegetative growth in F. culmorum. The chemical structures of phenols were constructed and partially optimised based on Molecular Mechanics (MM) studies and energy minimisation by Density Functional Theory (DFT). Docking analysis of the phenolic molecules was run on the 3D model of F. culmorum TRI5. Experimental biological activity, molecular descriptors and interacting-structures obtained from computational analysis were compared. Besides the catalytic domain, three privileged sites in the interaction with the inhibitory molecules were identified on the protein surface. The TRI5-ligand interactions highlighted in this study represent a powerful tool to the identification of new Fusarium-targeted molecules with potential as trichothecene inhibitors
Design, synthesis, molecular modeling and anti-HIV 1 integrase activity of a series of photoactivable diketo acid-containing inhibitors as affinity probes
Photoaffinity Labelling (PL) is a powerful method in the chemical proteomic approach of protein
functions. This method is especially useful for the identification of ligand-binding sites of
target proteins and for the investigation of ligand–receptor interactions. The use of affinity-labeled
inhibitors to covalently modify the site of interaction and subsequent analysis of the protein have
been very effective in providing useful informations about inhibitor binding for a multitude of
therapeutic target proteins. Therefore, it could reasonably be applied in drug discovery and
development processes.
For example, such approach can be used to obtain structural information detailing the association
between the enzyme HIV-1 integrase (IN) and inhibitors under development
Design and synthesis of bis-amide and hydrazide-containing derivatives of malonic acid as potential HIV-1 integrase inhibitors
HIV-1 integrase (IN) is an attractive and validated target for the development of novel therapeutics against AIDS. In the search for new IN inhibitors, we designed and synthesized three series of bis-amide and hydrazide-containing derivatives of malonic acid. We performed a docking study to investigate the potential interactions of the title compounds with essential amino acids on the IN active site
Factors Impacting σ- and π-Hole Regions as Revealed by the Electrostatic Potential and Its Source Function Reconstruction: The Case of 4,4'-Bipyridine Derivatives
Positive electrostatic potential (V) values are often associated with σ- and π-holes, regions
of lower electron density which can interact with electron-rich sites to form noncovalent interactions.
Factors impacting σ- and π-holes may thus be monitored in terms of the shape and values of the
resulting V. Further precious insights into such factors are obtained through a rigorous decomposition
of the V values in atomic or atomic group contributions, a task here achieved by extending the
Bader–Gatti source function (SF) for the electron density to V. In this article, this general methodology
is applied to a series of 4,4'-bipyridine derivatives containing atoms from Groups VI (S, Se) and VII
(Cl, Br), and the pentafluorophenyl group acting as a π-hole. As these molecules are characterized
by a certain degree of conformational freedom due to the possibility of rotation around the two
C–Ch bonds, from two to four conformational motifs could be identified for each structure through
conformational search. On this basis, the impact of chemical and conformational features on σ- and
Ï€-hole regions could be systematically evaluated by computing the V values on electron density
isosurfaces (VS) and by comparing and dissecting in atomic/atomic group contributions the VS
maxima (VS,max) values calculated for different molecular patterns. The results of this study confirm
that both chemical and conformational features may seriously impact σ- and π-hole regions and
provide a clear analysis and a rationale of why and how this influence is realized. Hence, the proposed
methodology might offer precious clues for designing changes in the σ- and π-hole regions, aimed at
affecting their potential involvement in noncovalent interactions in a desired way
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