A molecular docking-based comparative assessment of various anticholinergic drugs as antidotes to different nerve agent poisoning

Das, Bishwajit; Majumder, Durjoy

doi:10.1080/07391102.2022.2125904

Cited by 2 publications

(1 citation statement)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cholinergic syndrome is caused by the accumulation of acetylcholine in the body due to the inhibition of acetylcholinesterase [17]. It is estimated that about 15%-20% of patients who take irinotecan will experience diarrhea and myelosuppression.…”

Section: Introductionmentioning

confidence: 99%

"Cholinergic side Effect-Free anticancer drugs: paving the way for safer and more effective cancer treatment"

Ritu,

Chandra,

Das

2023

Journal of Biomolecular Structure and Dynamics

View full text Add to dashboard Cite

Cancer is a leading cause of mortality worldwide, and various anticancer medications have been developed that target different biological pathways involved in cancer growth and progression. Topoisomerase I (TOP1) is an essential enzyme involved in unwinding supercoiled DNA, and it serves as a key target for several anti-cancer drugs. Irinotecan, a semisynthetic derivative of camptothecin, is a potent topoisomerase I toxin that is effective at eliminating human tumor cells.However, irinotecan and other topoisomerase I inhibitors are known to cause cholinergic syndrome, which can lead to severe side effects in cancer patients. Further investigation has revealed that the acetylcholinesterase (AChE) enzyme plays a role in the development of cholinergic syndrome in irinotecan-treated patients. It appears that irinotecan or its metabolites directly interact with AChE, leading to an accumulation of acetylcholine and subsequent symptoms of cholinergic syndrome. Phytochemicals present in the plant Phyllanthus emblica, commonly known as amla, have been studied for their therapeutic effects on various diseases. This study focuses on targeting and inhibiting the TOP1 protein using the phytochemicals present in amla as a potential substitute treatment for cancer. In-silico studies were conducted to analyze the binding a nities of sixty three compounds towards the target TOP1 and AChE enzyme and check their drug likeness property using ADME. The six hit compounds with binding a nities similar to or better than their respective standard inhibitors were selected, and their stability was checked using molecular dynamic simulation. These ndings suggest that the development of novel anticancer medications that do not inhibit AChE or fresh Topoisomerase inhibitors based on the camptothecin scaffold may help alleviate the side effects of irinotecan.

show abstract

Section: Introductionmentioning

confidence: 99%

"Cholinergic side Effect-Free anticancer drugs: paving the way for safer and more effective cancer treatment"

Ritu,

Chandra,

Das

2023

Journal of Biomolecular Structure and Dynamics

View full text Add to dashboard Cite

show abstract

Cholinergic Side Effect-Free Anticancer Drugs: Paving the Way for Safer and More Effective Cancer Treatment

Ritu

Chandra

Das

2023

Preprint

View full text Add to dashboard Cite

Cancer is a leading cause of mortality worldwide, and various anticancer medications have been developed that target different biological pathways involved in cancer growth and progression. Topoisomerase I (TOP1) is an essential enzyme involved in unwinding supercoiled DNA, and it serves as a key target for several anti-cancer drugs. Irinotecan, a semi-synthetic derivative of camptothecin, is a potent topoisomerase I toxin that is effective at eliminating human tumor cells. However, irinotecan and other topoisomerase I inhibitors are known to cause cholinergic syndrome, which can lead to severe side effects in cancer patients. Further investigation has revealed that the acetylcholinesterase (AChE) enzyme plays a role in the development of cholinergic syndrome in irinotecan-treated patients. It appears that irinotecan or its metabolites directly interact with AChE, leading to an accumulation of acetylcholine and subsequent symptoms of cholinergic syndrome. Phytochemicals present in the plant Phyllanthus emblica, commonly known as amla, have been studied for their therapeutic effects on various diseases. This study focuses on targeting and inhibiting the TOP1 protein using the phytochemicals present in amla as a potential substitute treatment for cancer. In-silico studies were conducted to analyze the binding affinities of sixty three compounds towards the target TOP1 and AChE enzyme and check their drug likeness property using ADME. The six hit compounds with binding affinities similar to or better than their respective standard inhibitors were selected, and their stability was checked using molecular dynamic simulation. These findings suggest that the development of novel anticancer medications that do not inhibit AChE or fresh Topoisomerase inhibitors based on the camptothecin scaffold may help alleviate the side effects of irinotecan.

show abstract

A molecular docking-based comparative assessment of various anticholinergic drugs as antidotes to different nerve agent poisoning

Cited by 2 publications

References 42 publications

"Cholinergic side Effect-Free anticancer drugs: paving the way for safer and more effective cancer treatment"

"Cholinergic side Effect-Free anticancer drugs: paving the way for safer and more effective cancer treatment"

Cholinergic Side Effect-Free Anticancer Drugs: Paving the Way for Safer and More Effective Cancer Treatment

Contact Info

Product

Resources

About