Dual action anti‐inflammatory/antiviral isoquinoline alkaloids as potent naturally occurring anti‐SARS‐CoV‐2 agents: A combined pharmacological and medicinal chemistry perspective

Abstract

In the search for compounds that inhibit the SARS‐CoV‐2 after the onset of the COVID‐19 pandemic, isoquinoline‐containing alkaloids have been identified as compounds with high potential to fight the disease. In addition to having strong antiviral activities, most of these alkaloids have significant anti‐inflammatory effects which are often manifested through the inhibition of a promising host‐based anti‐COVID‐19 target, the p38 MAPK signaling pathway. In the present review, our pharmacological and medicinal chemistry evaluation resulted in highlighting the potential of anti‐SARS‐CoV‐2 isoquinoline‐based alkaloids for the treatment of COVID‐19 patients. Considering critical parameters of the antiviral and anti‐inflammatory activities, mechanism of action, as well as toxicity/safety profile, we introduce the alkaloids emetine, cephaeline, and papaverine as high‐potential therapeutic agents for use in the treatment of COVID‐19. Although preclinical studies confirm that some isoquinoline‐based alkaloids reviewed in this study have a high potential to inhibit the SARS‐CoV‐2, their entry into drug regimens of COVID‐19 patients requires further clinical trial studies and toxicity evaluation.

TRAIL of Hope: Bioactive Dietary Component-Driven Carrier-Free Nanoplatforms for Synergistically Enhanced Tumor Multimodal Therapy

“……”

TRAIL of Hope: Bioactive Dietary Component-Driven Carrier-Free Nanoplatforms for Synergistically Enhanced Tumor Multimodal Therapy

“……”

Anticancer and Anti‐Inflammatory Potential of Coptisine as a Planar Quaternary Benzo[C]Phenanthridine Alkaloid With G‐Quadruplex DNA Telomeric Induction Activity

“…As can be deduced from the results of the table, the level of cytotoxicity in jatrorrhizine (containing a hydroxyl group) is significantly reduced compared to other compounds. In our recent studies, we have explained the role of the hydroxyl group in reducing the toxicity of isoquinoline alkaloids (Valipour et al 2023;Valipour et al 2021).…”

“…The connections between this pathway activity and inflammation have been described in previous studies (Saklatvala 2004), and we have also recently described the role of the disproportionate activation of the p38 MAPK pathway in the occurrence of inflammatory disorders such as neuro‐inflammation (Valipour 2023; Valipour, Mohammadi, & Valipour 2023). We also introduced the modulation of this signaling pathway as one of the main mechanisms of the anti‐inflammatory effects of isoquinoline alkaloids (a class of alkaloids to which coptisine belongs) (Valipour et al 2023). In another study, we proposed that the therapeutic effects of drugs whose side effects are exerted through inappropriate activation of the p38 MAPK pathway (such as emetine) can be managed by coadministration with proper p38 MAPK inhibitors (Valipour et al 2022).…”

Recent Advances in Synthetic Isoquinoline-Based Derivatives in Drug Design

“…Research has shown that natural isoquinoline alkaloids display the potential to work on multiple mechanisms associated with inflammation. In this context, much of the efforts are focused on isoquinolines as synthetic analogs of these natural substances [ 224 , 225 , 226 , 227 , 228 , 229 , 230 , 231 , 232 ].…”

TRAIL of Hope: Bioactive Dietary Component-Driven Carrier-Free Nanoplatforms for Synergistically Enhanced Tumor Multimodal Therapy

“……”

Anticancer and Anti‐Inflammatory Potential of Coptisine as a Planar Quaternary Benzo[C]Phenanthridine Alkaloid With G‐Quadruplex DNA Telomeric Induction Activity

“…As can be deduced from the results of the table, the level of cytotoxicity in jatrorrhizine (containing a hydroxyl group) is significantly reduced compared to other compounds. In our recent studies, we have explained the role of the hydroxyl group in reducing the toxicity of isoquinoline alkaloids (Valipour et al 2023;Valipour et al 2021).…”

“…The connections between this pathway activity and inflammation have been described in previous studies (Saklatvala 2004), and we have also recently described the role of the disproportionate activation of the p38 MAPK pathway in the occurrence of inflammatory disorders such as neuro‐inflammation (Valipour 2023; Valipour, Mohammadi, & Valipour 2023). We also introduced the modulation of this signaling pathway as one of the main mechanisms of the anti‐inflammatory effects of isoquinoline alkaloids (a class of alkaloids to which coptisine belongs) (Valipour et al 2023). In another study, we proposed that the therapeutic effects of drugs whose side effects are exerted through inappropriate activation of the p38 MAPK pathway (such as emetine) can be managed by coadministration with proper p38 MAPK inhibitors (Valipour et al 2022).…”

Recent Advances in Synthetic Isoquinoline-Based Derivatives in Drug Design

“…Research has shown that natural isoquinoline alkaloids display the potential to work on multiple mechanisms associated with inflammation. In this context, much of the efforts are focused on isoquinolines as synthetic analogs of these natural substances [ 224 , 225 , 226 , 227 , 228 , 229 , 230 , 231 , 232 ].…”

TRAIL of Hope: Bioactive Dietary Component-Driven Carrier-Free Nanoplatforms for Synergistically Enhanced Tumor Multimodal Therapy

“……”

Anticancer and Anti‐Inflammatory Potential of Coptisine as a Planar Quaternary Benzo[C]Phenanthridine Alkaloid With G‐Quadruplex DNA Telomeric Induction Activity

“…As can be deduced from the results of the table, the level of cytotoxicity in jatrorrhizine (containing a hydroxyl group) is significantly reduced compared to other compounds. In our recent studies, we have explained the role of the hydroxyl group in reducing the toxicity of isoquinoline alkaloids (Valipour et al 2023;Valipour et al 2021).…”

“…The connections between this pathway activity and inflammation have been described in previous studies (Saklatvala 2004), and we have also recently described the role of the disproportionate activation of the p38 MAPK pathway in the occurrence of inflammatory disorders such as neuro‐inflammation (Valipour 2023; Valipour, Mohammadi, & Valipour 2023). We also introduced the modulation of this signaling pathway as one of the main mechanisms of the anti‐inflammatory effects of isoquinoline alkaloids (a class of alkaloids to which coptisine belongs) (Valipour et al 2023). In another study, we proposed that the therapeutic effects of drugs whose side effects are exerted through inappropriate activation of the p38 MAPK pathway (such as emetine) can be managed by coadministration with proper p38 MAPK inhibitors (Valipour et al 2022).…”

Recent Advances in Synthetic Isoquinoline-Based Derivatives in Drug Design

“…Research has shown that natural isoquinoline alkaloids display the potential to work on multiple mechanisms associated with inflammation. In this context, much of the efforts are focused on isoquinolines as synthetic analogs of these natural substances [ 224 , 225 , 226 , 227 , 228 , 229 , 230 , 231 , 232 ].…”