ADME/PK Insights of Crocetin: A Molecule Having an Unusual Chemical Structure with Druglike Features
Diksha Manhas, Sumit Dhiman, Harpreet Kour, Dilpreet Kour, Kuhu Sharma, Priya Wazir, Bhavna Vij, Ajay Kumar, Sanghapal D. Sawant, Zabeer Ahmed, Utpal Nandi
Abstract
High Resolution Image Download MS PowerPoint Slide Crocetin is a promising phyto-based molecule to treat Alzheimer’s disease (AD). The chemical structure of crocetin is incongruent with various standard structural features of CNS drugs. As poor pharmacokinetic behavior is the major hurdle for any candidate to become a drug, we elucidated its druggable characteristics by implementing in silico, in vitro, and in vivo approaches, as limited ADME/PK information is available. Results demonstrate several attributes of crocetin based on rules of drug-likeness, lipophilicity, p K a, P-gp inhibitory activity, plasma stability, RBC partitioning, metabolic stability, CYP inhibitory action, blood-brain barrier (BBB) permeability, oral bioavailability, and pharmacokinetic interaction with marketed anti-Alzheimer’s drugs (memantine, donepezil, galantamine, and rivastigmine). However, aqueous solubility, chemical stability, plasma protein binding, and P-gp induction are some concerns associated with this molecule that should be taken into consideration during its further development. Overall results indicate favorable ADME/PK behavior and potential druggable candidature of crocetin.