The potential rewarding and reinforcing effects of the substituted benzofurans 2-EAPB and 5-EAPB in rodents

Sayson, Leandro Val; Custodio, Raly James Perez; Ortiz, Darlene Mae; Lee, Hyun Jun; Kim, Mi-Kyung; Jeong, Youngdo; Lee, Yong Sup; Kim, Hee Jin; Cheong, Jae Hoon

doi:10.1016/j.ejphar.2020.173527

Cited by 11 publications

(9 citation statements)

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“…The direct formylation of electron-rich arenes can be conveniently accomplished via the Vilsmeier–Haack (V–H) reaction. Indeed, the benzo[b]furan nucleus is reported to yield the 2-formyl derivative by reaction with the V–H electrophilic species [ 47 ]. We anticipated that the regioselectivity of the V–H reaction could change if electron-donating groups were present on the phenyl ring of the benzo-fused system.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and NLRP3-Inflammasome Inhibitory Activity of the Naturally Occurring Velutone F and of Its Non-Natural Regioisomeric Chalconoids

Ventura

Perrone

Missiroli

et al. 2022

IJMS

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Plant-derived remedies rich in chalcone-based compounds have been known for centuries in the treatment of specific diseases, and nowadays, the fascinating chalcone framework is considered a useful and, above all, abundant natural chemotype. Velutone F, a new chalconoid from Millettia velutina, exhibits a potent effect as an NLRP3-inflammasome inhibitor; the search for new natural/non-natural lead compounds as NLRP3 inhibitors is a current topical subject in medicinal chemistry. The details of our work toward the synthesis of velutone F and the unknown non-natural regioisomers are herein reported. We used different synthetic strategies both for the construction of the distinctive benzofuran nucleus (BF) and for the key phenylpropenone system (PhP). Importantly, we have disclosed a facile entry to the velutone F via synthetic routes that can also be useful for preparing non-natural analogs, a prerequisite for extensive SAR studies on the new flavonoid class of NLRP3-inhibitors.

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Section: Resultsmentioning

confidence: 99%

Synthesis and NLRP3-Inflammasome Inhibitory Activity of the Naturally Occurring Velutone F and of Its Non-Natural Regioisomeric Chalconoids

Ventura

Perrone

Missiroli

et al. 2022

IJMS

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“…Procedure: This method was based on previous studies with some modifications ( Kim et al ., 2019 ; Custodio et al ., 2020 ; Sayson et al ., 2020 ). The test consisted of three phases: (A) habituation (days 1-3) and pre-conditioning (day 4; 15 min), (B) conditioning (days 5-12; 30 min), and (C) post-conditioning (day 13; 15 min).…”

Section: Methodsmentioning

confidence: 99%

Differentially Expressed Genes in Period 2-Overexpressing Mice Striatum May Underlie Their Lower Sensitivity to Methamphetamine Addiction-Like Behavior

Sayson

Kim

Jeon

et al. 2022

Biomol Ther (Seoul)

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Previous reports have demonstrated that genetic mechanisms greatly mediate responses to drugs of abuse, including methamphetamine (METH). The circadian gene Period 2 ( Per2 ) has been previously associated with differential responses towards METH in mice. While the behavioral consequences of eliminating Per2 have been illustrated previously, Per2 overexpression has not yet been comprehensively described; although, Per2 -overexpressing ( Per2 OE) mice previously showed reduced sensitivity towards METH-induced addiction-like behaviors. To further elucidate this distinct behavior of Per2 OE mice to METH, we identified possible candidate biomarkers by determining striatal differentially expressed genes (DEGs) in both drug-naïve and METH-treated Per2 OE mice relative to wild-type (WT), through RNA sequencing. Of the several DEGs in drug naïve Per2 OE mice, we identified six genes that were altered after repeated METH treatment in WT mice, but not in Per2 OE mice. These results, validated by quantitative real-time polymerase chain reaction, could suggest that the identified DEGs might underlie the previously reported weaker METH-induced responses of Per2 OE mice compared to WT. Gene network analysis also revealed that Asic3 , Hba-a1 , and Rnf17 are possibly associated with Per2 through physical interactions and predicted correlations, and might potentially participate in addiction. Inhibiting the functional protein of Asic3 prior to METH administration resulted in the partial reduction of METH-induced conditioned place preference in WT mice, supporting a possible involvement of Asic3 in METH-induced reward. Although encouraging further investigations, our findings suggest that these DEGs, including Asic3 , may play significant roles in the lower sensitivity of Per2 OE mice to METH.

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“…(1, 3, and 10 mg/kg), KET (5 and 10 mg/kg), and saline (SAL) during the conditioning phase and were confined to a randomly designated compartment of the drug-paired compartment for 30 min as done in previous studies. [13][14][15] Separate cohorts of mice (n = 10/group) were injected with SCH (0.5 mg/kg), HAL (0.2 mg/kg), or SAL, 30 min before conditioning sessions with the drugs mentioned above in order to examine the involvement of DRD1 and DRD2 in the rewarding effects of drugs. The mice received SAL and were placed in the nondrug-paired compartment on alternate days.…”

Section: Methodsmentioning

confidence: 99%

“…their rewarding and reinforcing. 13,14,17 Specifically, CPP gauges the conditioned rewarding value of drugs by measuring the time spent by a subject in the drug-paired compartment versus the vehicle (VEH)paired one. 15,16 The SA test assesses the reinforcing efficacy of substances by counting the number of times a subject elicits the lever response that results in drug infusion.…”

Section: Methodsmentioning

confidence: 99%

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The dopaminergic alterations induced by 4‐F‐PCP and 4‐Keto‐PCP may enhance their drug‐induced rewarding and reinforcing effects: Implications for abuse

et al. 2020

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Novel psychoactive substances remain the popular recreational drugs of use over the years. They continue to bypass government restrictions due to their synthesis and modifications. Recent additions to the lists are the 4‐F‐PCP and 4‐Keto‐PCP, analogs of the drug phencyclidine (PCP) known to induce adverse effects and abuse potential. However, studies on the abuse potential of 4‐F‐PCP and 4‐Keto‐PCP remain scarce. The rewarding and reinforcing effects of the drugs were assessed using conditioned place preference (CPP), self‐administration, and locomotor sensitization tests. Dopamine (DA) receptor antagonists (SCH23390 and haloperidol) were administered during CPP to evaluate the involvement of the mesolimbic dopaminergic system. DA‐related protein expression in the nucleus accumbens (NAcc) and ventral tegmental area (VTA) was measured. Additionally, phosphorylated cyclic‐adenosine monophosphate‐activated protein (AMP) response element‐binding (p‐CREB) protein, deltaFosB (∆FosB), and brain‐derived neurotrophic factor (BDNF) protein levels in the NAcc were measured to assess the addiction neural plasticity effect of the drugs. Both 4‐F‐PCP and 4‐Keto‐PCP‐induced CPP and self‐administration; however, only 4‐F‐PCP elicited locomotor sensitization. Treatment with DA receptor antagonists (SH23390 and haloperidol) inhibited the 4‐F‐ and 4‐Keto‐induced CPP. Both substances altered the levels of DA receptor D1 (DRD1), thyroxine hydroxylase (TH), DA receptor D2 (DRD2), p‐CREB, ∆FosB, and BDNF. The results suggest that 4‐F‐PCP and 4‐Keto‐PCP may induce abuse potential in rodents via alterations in dopaminergic system accompanied by addiction neural plasticity.

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The potential rewarding and reinforcing effects of the substituted benzofurans 2-EAPB and 5-EAPB in rodents

Cited by 11 publications

References 50 publications

Synthesis and NLRP3-Inflammasome Inhibitory Activity of the Naturally Occurring Velutone F and of Its Non-Natural Regioisomeric Chalconoids

Synthesis and NLRP3-Inflammasome Inhibitory Activity of the Naturally Occurring Velutone F and of Its Non-Natural Regioisomeric Chalconoids

Differentially Expressed Genes in Period 2-Overexpressing Mice Striatum May Underlie Their Lower Sensitivity to Methamphetamine Addiction-Like Behavior

The dopaminergic alterations induced by 4‐F‐PCP and 4‐Keto‐PCP may enhance their drug‐induced rewarding and reinforcing effects: Implications for abuse

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