Design, synthesis and biological evaluation of naphthalene-derived (arylalkyl)azoles containing heterocyclic linkers as new anticonvulsants: A comprehensive in silico, in vitro, and in vivo study

Valipour, Mehdi; Naderi, Nima; Heidarli, Elmira; Shaki, Fatemeh; Motafeghi, Farzaneh; Amiri, Fereshteh Talebpour; Emami, Saeed; Irannejad, Hamid

doi:10.1016/j.ejps.2021.105974

Cited by 13 publications

(5 citation statements)

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“…In that study, it was shown that tanshinone IIA can significantly inhibit pentylenetetrazole (PTZ)‐induced seizures. Since we have repeatedly used this model to investigate the anticonvulsant effects of our new compounds, we know that protection against PTZ‐induced seizures (at doses in the range of 100 mg/kg) is difficult and that only compounds with remarkable anticonvulsant activity can inhibit this type of seizure (Emami et al, 2021; Valipour, Naderi, et al, 2021).…”

Section: Cns‐active P38 Mapk Inhibitorsmentioning

confidence: 99%

Therapeutic prospects of naturally occurring p38 MAPK inhibitors tanshinone IIA and pinocembrin for the treatment of SARS‐CoV‐2‐induced CNS complications

Valipour

2023

Phytotherapy Research

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P38 mitogen‐activated protein kinase (p38 MAPK) signaling pathway is closely related to severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) replication and hyperinflammatory responses in coronavirus disease 2019 (COVID‐19). Therefore, blood–brain barrier‐penetrating p38 MAPK inhibitors have good potential for the treatment of central nervous system (CNS) complications of COVID‐19. The aim of the present study is the characterization of the therapeutic potential of tanshinone IIA and pinocembrin for the treatment of CNS complications of COVID‐19. Studies published in high‐quality journals indexed in databases Scopus, Web of Science, PubMed, and so forth were used to review the therapeutic capabilities of selected compounds. In continuation of our previous efforts to identify agents with favorable activity/toxicity profiles for the treatment of COVID‐19, tanshinone IIA and pinocembrin were identified with a high ability to penetrate the CNS. Considering the nature of the study, no specific time frame was determined for the selection of studies, but the focus was strongly on studies published after the emergence of COVID‐19. By describing the association of COVID‐19‐induced CNS disorders with p38 MAPK pathway disruption, this study concludes that tanshinone IIA and pinocembrin have great potential for better treatment of these complications. The inclusion of these compounds in the drug regimen of COVID‐19 patients requires confirmation of their effectiveness through the conduction of high‐quality clinical trials.

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Section: Cns‐active P38 Mapk Inhibitorsmentioning

confidence: 99%

Therapeutic prospects of naturally occurring p38 MAPK inhibitors tanshinone IIA and pinocembrin for the treatment of SARS‐CoV‐2‐induced CNS complications

Valipour

2023

Phytotherapy Research

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“…On the other hand, in the structure of both compounds, there is a naphthyl moiety that is attached to a nitrogen atom through a short linker. Naphthalene is a versatile platform in medicinal chemistry that is commonly used to increase the lipophilicity of molecules and facilitate penetration into the blood-brain barrier (BBB) [ 42 , 43 ]. These structural features have been investigated extensively in the subsequent optimizations and SAR studies discussed below.…”

Section: Inhibitory Effects Of Chalcone-amides Against Sars-cov and S...mentioning

confidence: 99%

Chalcone-amide, a privileged backbone for the design and development of selective SARS-CoV/SARS-CoV-2 papain-like protease inhibitors

Valipour

2022

European Journal of Medicinal Chemistry

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“…However, if compound 45 interacts at the active site of the PLpro, it is not clear how the structure directs in the active site. Using the insights obtained from the crystallographic evaluations, the role of the naphthyl moiety (which is an important lipophilic scaffold in medicinal chemistry; Valipour, Naderi, et al, 2021 ) in the orientation of compound 45 in a similar pattern to that of compound 43 in the active site of the PLpro is critical. Accordingly, the naphthyl moiety is most likely located inside a lipophilic pocket containing Pro248 and Pro249 residues (see the interactions represented in the crystal structure of PLpro bound to some potent N‐BPC‐based inhibitors with the PDB codes of 4OVZ, 4OW0, 3MJ5, 3E9S, and 7E35).…”

Section: Benefits Of Using Cysteine Reactive Warheads In the Structur...mentioning

confidence: 99%

Recruitment of chalcone's potential in drug discovery of anti‐SARS‐CoV‐2 agents

Valipour

2022

Phytotherapy Research

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Chalcone is an interesting scaffold found in the structure of many naturally occurring molecules. Medicinal chemists are commonly interested in designing new chalconebased structures because of having the α, β-unsaturated ketone functional group, which allows these compounds to participate in Michael's reaction and create strong covalent bonds at the active sites of the targets. Some studies have identified several natural chalcone-based compounds with the ability to inhibit the severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus proteases. A few years after the advent of the coronavirus disease 2019 pandemic and the publication of many findings in this regard, there is some evidence that suggests chalcone scaffolding has great potential for use in the design and development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inhibitors. Artificial placement of this scaffold in the structure of optimized anti-SARS-CoV-2 compounds can potentially provide irreversible inhibition of the viral cysteine proteases 3-chymotrypsin-like protease and papain-like protease by creating Michael interaction. Despite having remarkable capabilities, the use of chalcone scaffold in drug design and discovery of SARS-CoV-2 inhibitors seems to have been largely neglected. This review addresses issues that could lead to further consideration of chalcone scaffolding in the structure of SARS-CoV-2 protease inhibitors in the future.

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Design, synthesis and biological evaluation of naphthalene-derived (arylalkyl)azoles containing heterocyclic linkers as new anticonvulsants: A comprehensive in silico, in vitro, and in vivo study

Cited by 13 publications

References 54 publications

Therapeutic prospects of naturally occurring p38 MAPK inhibitors tanshinone IIA and pinocembrin for the treatment of SARS‐CoV‐2‐induced CNS complications

Therapeutic prospects of naturally occurring p38 MAPK inhibitors tanshinone IIA and pinocembrin for the treatment of SARS‐CoV‐2‐induced CNS complications

Chalcone-amide, a privileged backbone for the design and development of selective SARS-CoV/SARS-CoV-2 papain-like protease inhibitors

Recruitment of chalcone's potential in drug discovery of anti‐SARS‐CoV‐2 agents

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