In silico evaluation of human small heat shock protein HSP27: Homology modeling, mutation analyses and docking studies

Fossa, Paola; Cichero, Elena

doi:10.1016/j.bmc.2015.04.070

Cited by 26 publications

(21 citation statements)

References 41 publications

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“…Finally, the protein–ligand complex stability was successfully assessed using a short (≈1 ps) molecular dynamics (MD) run at constant temperature, followed by an all‐atom energy minimization (LowModeMD using MOE software). This module allowed us to perform an exhaustive conformational analysis of the ligand–receptor binding site complex, as discussed in our other case studies, where it proved to be useful for preliminary evaluation of docking poses …”

Section: Methodsmentioning

confidence: 99%

Structure–Activity Relationships within a Series of σ₁ and σ₂ Receptor Ligands: Identification of a σ₂ Receptor Agonist (BS148) with Selective Toxicity against Metastatic Melanoma

et al. 2017

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A new series of spirocyclic σ receptor (σR) ligands were prepared and studied. Most were found to have a high affinity and selectivity for σ R; three compounds were shown to be σ R agonists, while another proved to be the only σ R antagonist. Only one of the σ R agonists (BS148) also exhibited σ R selectivity and was able to inhibit the growth of metastatic malignant melanoma cell lines without affecting normal human melanocytes. The antiproliferative activity of this compound suggested an σ R agonist profile. Further, preliminary investigations indicated that the mechanism of metastatic malignant melanoma cell death induced by BS148 is due, at least in part, to apoptosis.

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Section: Methodsmentioning

confidence: 99%

Structure–Activity Relationships within a Series of σ₁ and σ₂ Receptor Ligands: Identification of a σ₂ Receptor Agonist (BS148) with Selective Toxicity against Metastatic Melanoma

et al. 2017

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“…Since most compounds were not cytotoxic at 100 mM (the highest concentration tested), the selectivity index, i.e. ratio of MCC to EC 50 , was calculated to be at least 10,000 for the most active analogues 11, 14 and 16. These compounds inhibited RSV replication at nanomolar concentrations, far surpassing the antiviral activity of ribavirin (EC 50 ¼ 5.8 mM, SI > 43).…”

Section: Inhibition Of Rsvmentioning

confidence: 99%

Host dihydrofolate reductase (DHFR)-directed cycloguanil analogues endowed with activity against influenza virus and respiratory syncytial virus

Tonelli

Naesens

Gazzarrini

et al. 2017

European Journal of Medicinal Chemistry

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We have identified a series of 1-aryl-4,6-diamino-1,2-dihydrotriazines, structurally related to the antimalarial drug cycloguanil, as new inhibitors of influenza A and B virus and respiratory syncytial virus (RSV) via targeting of the host dihydrofolate reductase (DHFR) enzyme. Most analogues proved active against influenza B virus in the low micromolar range, and the best compounds (11, 13, 14 and 16) even reached the sub-micromolar potency of zanamivir (EC = 0.060 μM), and markedly exceeded (up to 327 times) the antiviral efficacy of ribavirin. Activity was also observed for two influenza A strains, including a virus with the S31N mutant form of M2 proton channel, which is the most prevalent resistance mutation for amantadine. Importantly, the compounds displayed nanomolar activity against RSV and a superior selectivity index, since the ratio of cytotoxic to antiviral concentration was >10,000 for the three most active compounds 11, 14 and 16 (EC ∼0.008 μM), far surpassing the potency and safety profile of the licensed drug ribavirin (EC = 5.8 μM, SI > 43).

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“…Then, the stability of the selected protein–ligand complexes was assessed using a short ~1 ps run of molecular dynamics (MD) at constant temperature, followed by an all‐atom energy minimization (LowModeMD implemented in moe software). This kind of module allowed to perform an exhaustive conformational analysis of the ligand–receptor binding site subset, as we previously reported about other case studies [22e,30]…”

Section: Methodsmentioning

confidence: 99%

Novel pyrrolocycloalkylpyrazole analogues as CB₁ ligands

Asproni

Manca²,

Pinna

et al. 2017

Chem Biol Drug Des

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Novel 1,4-dihydropyrazolo [3,4-a]pyrrolizine-, 4,5-dihydro-1H-pyrazolo [4,3-g]indolizine-and 1,4,5,6-tetrahydropyrazolo[3,4-c]pyrrolo [1,2-a]azepine-3-carboxamidebased compounds were designed and synthesized for cannabinoid CB 1 and CB 2 receptor interactions. Any of the new synthesized compounds showed high affinity for CB 2 receptor with K i values superior to 314 nm, whereas some of them showed moderate affinity for CB 1 receptor with K i values inferior to 400 nm. 7-Chloro-1-(2,indolizine-3-carboxamide (2j) exhibited good affinity for CB 1 receptor (K i CB 1 = 81 nm) and the highest CB 2 /CB 1 selectively ratio (>12). Docking studies carried out on such compounds were performed using the hCB 1 X-ray in complex with the close pyrazole analogue AM6538 and disclosed specific pattern of interactions related to the tricyclic pyrrolopyrazole scaffolds as CB 1 ligands.

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In silico evaluation of human small heat shock protein HSP27: Homology modeling, mutation analyses and docking studies

Cited by 26 publications

References 41 publications

Structure–Activity Relationships within a Series of σ₁ and σ₂ Receptor Ligands: Identification of a σ₂ Receptor Agonist (BS148) with Selective Toxicity against Metastatic Melanoma

Structure–Activity Relationships within a Series of σ₁ and σ₂ Receptor Ligands: Identification of a σ₂ Receptor Agonist (BS148) with Selective Toxicity against Metastatic Melanoma

Host dihydrofolate reductase (DHFR)-directed cycloguanil analogues endowed with activity against influenza virus and respiratory syncytial virus

Novel pyrrolocycloalkylpyrazole analogues as CB₁ ligands

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In silico evaluation of human small heat shock protein HSP27: Homology modeling, mutation analyses and docking studies

Cited by 26 publications

References 41 publications

Structure–Activity Relationships within a Series of σ1 and σ2 Receptor Ligands: Identification of a σ2 Receptor Agonist (BS148) with Selective Toxicity against Metastatic Melanoma

Structure–Activity Relationships within a Series of σ1 and σ2 Receptor Ligands: Identification of a σ2 Receptor Agonist (BS148) with Selective Toxicity against Metastatic Melanoma

Host dihydrofolate reductase (DHFR)-directed cycloguanil analogues endowed with activity against influenza virus and respiratory syncytial virus

Novel pyrrolocycloalkylpyrazole analogues as CB1 ligands

Contact Info

Product

Resources

About

Structure–Activity Relationships within a Series of σ₁ and σ₂ Receptor Ligands: Identification of a σ₂ Receptor Agonist (BS148) with Selective Toxicity against Metastatic Melanoma

Structure–Activity Relationships within a Series of σ₁ and σ₂ Receptor Ligands: Identification of a σ₂ Receptor Agonist (BS148) with Selective Toxicity against Metastatic Melanoma

Novel pyrrolocycloalkylpyrazole analogues as CB₁ ligands