Activity of Mannich bases of 7-hydroxycoumarin against Flaviviridae

Mazzei, Mauro; Nieddu, Erika; Miele, Mariangela; Balbi, Alessandro; Ferrone, Marco; Fermeglia, Maurizio; Mazzei, Marco T.; Pricl, Sabrina; Colla, Paolo La; Marongiu, Fabio; Ibba, Cristina; Loddo, Roberta

doi:10.1016/j.bmc.2007.11.045

Cited by 54 publications

(38 citation statements)

References 66 publications

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“…Accordingly, it follows that the association between the ligands and the RdRp is mainly driven by more favorable nonpolar interactions in the complex than in the solution, in harmony with a proposed general scheme for noncovalent association. 33,34 However, as indicated for instance by the energy components of compound 2, this driving force can be weakened when the polar groups on the molecule do not find an adequate bonding pattern in the protein compared to water. The free energy penalty for this (DE el + DG PB ) term is least for compound 1 and this, together with its substantial van der Waals contribution and moderate entropic unfavorable term, consequently leads to one of the highest binding affinity in this set of inhibitors.…”

Section: Modeling Of the A-c Series Of Compounds Versus Bvdv Rdrpmentioning

confidence: 98%

“…An unsubstituted aromatic ring can be found in active (1, 7, 9, 21, 25, 52, 54-56) and inactive (13,34,45) compounds, while the presence of electron-releasing groups as CH 3 and OCH 3 (32,42) or of a benzyl residue (15,22) is always detrimental for the expression of activity.…”

Section: Structure-activity Relationshipsmentioning

confidence: 99%

“…The optimized structures of the inhibitors were docked into the putative enzyme allosteric binding site by applying a consolidated procedure; 33,34 accordingly, it will be briefly reported below. The software AUTODOCK 3.0 44 was employed to estimate the possible binding orientations of all compounds in the receptor.…”

Section: Molecular Modelingmentioning

confidence: 99%

“…33,34 In this case, 1 ns MD simulation at 310 K were employed to sample the conformational space of the substrate-enzyme complex in the GB/SA continuum solvation environment. The integration step was equal to 1 fs and the parm99 force field parameters were applied in the simulations.…”

Section: Molecular Modelingmentioning

confidence: 99%

“…A conformational search was carried out using a well-validated, ad-hoc developed combined molecular mechanics/molecular dynamics simulated annealing (MDSA) protocol. 33,34 Accordingly, the relaxed structures were subjected to five repeated temperature cycles (from 310 K to 1000 K and back) using constant volume/constant temperature (NVT) MD conditions. At the end of each annealing cycle, the structures were again energy minimized to converge below 10 À4 kcal/ (mol Å), and only the structures corresponding to the minimum energy were used for further modeling.…”

Section: Molecular Modelingmentioning

confidence: 99%

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Antiviral and cytotoxic activities of aminoarylazo compounds and aryltriazene derivatives

Tonelli

Vazzana

Tasso

et al. 2009

Bioorganic & Medicinal Chemistry

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Twelve aminoarylazocompounds (A-C) and 46 aryltriazene 7 derivatives (D-G) have been synthesized and evaluated in cell-based assays for cytotoxicity and antiviral activity against a panel of 10 RNA and DNA viruses. Eight aminoazocompounds and 27 aryltriazene derivatives exhibited antiviral activity, sometimes of high level, against one or more viruses. A marked activity against BVDV and YFV was prevailing among the former compounds, while the latter type of compounds affected mainly CVB-2 and RSV. None of the active compounds inhibited the multiplication of HIV-1, VSV and VV. Arranged in order of decreasing potency and selectivity versus the host cell lines, the best compounds are the following; BVDV: 1>7>8>4; YFV: 7>5; CVB-2: 25>56>18; RSV: 14>20>55>38>18>19; HSV-1: 2. For these compounds the EC(50) ranged from 1.6 microM (1) to 12 microM (18), and the S. I. from 19.4 (1) to 4.2 (2). Thus the aminoarylazo and aryltriazene substructures appear as interesting molecular component for developing antiviral agents against ss RNA viruses, particularly against RSV and BVDV, which are important human and veterinary pathogens. Finally, molecular modeling investigations indicated that compounds of structure A-C, active against BVDV, could work targeting the viral RNA-dependent RNA-polymerase (RdRp), having been observed a good agreement between the trends of the estimated IC(50) and the experimental EC(50) values.

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Section: Modeling Of the A-c Series Of Compounds Versus Bvdv Rdrpmentioning

confidence: 98%

Section: Structure-activity Relationshipsmentioning

confidence: 99%

Section: Molecular Modelingmentioning

confidence: 99%

Section: Molecular Modelingmentioning

confidence: 99%

Section: Molecular Modelingmentioning

confidence: 99%

See 3 more Smart Citations

Antiviral and cytotoxic activities of aminoarylazo compounds and aryltriazene derivatives

Tonelli

Vazzana

Tasso

et al. 2009

Bioorganic & Medicinal Chemistry

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Piperazine and piperidine‐substituted 7‐hydroxy coumarins for the development of anti‐inflammatory agents

Buran

Reıs

Sipahi

et al. 2021

Archiv der Pharmazie

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Coumarins (2H‐1‐benzopyran‐2‐one), derivatives that can be isolated from several plants, have been reported for their anticoagulant, antimicrobial, anti‐inflammatory, or anticancer activity. Some of these structures are currently approved for the treatment of cardiovascular diseases, as antibiotics or as an anticancer drug. Given the great potential of this structure and the limited number of studies that focus on molecules derived from carbon 8 of the benzopyranone heterocycle, we synthesized in this project 38 coumarin derivatives by substituting carbon 8 of the benzopyran ring with some aromatic and aliphatically substituted piperidines and piperazines. As a few of these structures were already shown to exhibit some carbonic anhydrase (CA) inhibition and as CA enzymes are reported to be closely related to inflammation, the synthesized derivatives were evaluated for their anti‐inflammatory activity in vitro. The results indicated that compounds 20 and 31 revealed promising anti‐inflammatory activity, as they demonstrated better activity than the reference drugs.

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A Complete Multiscale Modelling Approach for Polymer–Clay Nanocomposites

Scocchi

Posocco

Handgraaf

et al. 2009

Chemistry A European J

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We present an innovative, multiscale computational approach to probe the behaviour of polymer-clay nanocomposites (PCNs). Our modeling recipe is based on 1) quantum/force-field-based atomistic simulation to derive interaction energies among all system components; 2) mapping of these values onto mesoscopic bead-field (MBF) hybrid-method parameters; 3) mesoscopic simulations to determine system density distributions and morphologies (i.e., intercalated versus exfoliated); and 4) simulations at finite-element levels to calculate the relative macroscopic properties. The entire computational procedure has been applied to two well-known PCN systems, namely Nylon 6/Cloisite 20A and Nylon 6/Cloisite 30B, as test materials, and their mechanical properties were predicted in excellent agreement with the available experimental data. Importantly, our methodology is a truly bottom-up approach, and no "learning from experiment" was needed in any step of the entire procedure.

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Activity of Mannich bases of 7-hydroxycoumarin against Flaviviridae

Cited by 54 publications

References 66 publications

Antiviral and cytotoxic activities of aminoarylazo compounds and aryltriazene derivatives

Antiviral and cytotoxic activities of aminoarylazo compounds and aryltriazene derivatives

Piperazine and piperidine‐substituted 7‐hydroxy coumarins for the development of anti‐inflammatory agents

A Complete Multiscale Modelling Approach for Polymer–Clay Nanocomposites

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