Exploring β-Tubulin Inhibitors from Plant Origin using Computational Approach

Area of Science:

• Computational chemistry
• Drug discovery
• Natural products

Background:

• Beta-tubulin is a key target for anti-cancer drugs like paclitaxel.
• Mutations in beta-tubulin can lead to resistance against chemotherapy.
• Specific mutations confer high resistance to paclitaxel binding.

Purpose of the Study:

• To identify novel beta-tubulin inhibitors from natural sources, specifically alkaloids.
• To utilize a virtual screening approach for discovering potential anti-cancer agents.

Main Methods:

• Virtual screening of the NPACT database for alkaloids.
• Pharmacokinetic and toxicity risk assessment using Molinspiration and DataWarrior.
• Binding efficiency analysis with beta-tubulin using AutoDock.
• Oral toxicity prediction and metabolic capacity assessment.
• Scaffold analysis for compound synthesis.

Main Results:

• Isostrychnine, from Strychnosnux-vomica, demonstrated favorable pharmacokinetic and bioavailability properties.
• Isostrychnine exhibited efficient binding with beta-tubulin.
• Isostrychnine shows promise for treating paclitaxel-resistant cancers.

Conclusions:

• This study is the first to report isostrychnine's inhibitory activity against beta-tubulin.
• Isostrychnine is a potential lead compound for developing new cancer therapies.
• Further experimental validation is recommended.