Towards the Development of Anticancer Drugs from Andrographolide: Semisynthesis, Bioevaluation, QSAR Analysis and Pharmacokinetic Studies

Title:Towards the Development of Anticancer Drugs from Andrographolide: Semisynthesis, Bioevaluation, QSAR Analysis and Pharmacokinetic Studies

Volume: 15 Issue: 11

Author(s): Abhijit Hazra, Chanchal Mondal, Debanjana Chakraborty, Amit K. Halder, Yogesh P. Bharitkar, Susanta K. Mondal, Sukdeb Banerjee, Tarun Jha and Nirup B. Mondal

Affiliation:

Keywords: 1, 3-dipolar cycloaddition, 2D and 3D QSAR, Andrographolide, Anticancer, Dispiro-pyrrolidino/ pyrrolizidinooxindole, Pharmacokinetics.

Abstract: Isolation of andrographolide from Andrographis paniculata, preparation of a library of derivatives via 1,3-dipolar cycloaddition of andrographolide with azomethine ylides generated from isatin derivatives or acenaphthoquinone and seconday α-amino acids, evaluation of the anticancer potential of the products, quantitative structure activity relationship studies and pharmacokinetic parameter determination have been described. 2D QSAR studies revaled that steric effects and van der Waals interactions play major roles in the determination of antiproliferative activity of these derivatives. 3D QSAR study predicted that the benzyl substitution at N₂₀ position may be important for higher steric interaction. Pharmacokinetic studies with two most potent analogues revealed moderate chemical stability but poor aqueous solubility, metabolic stability and permeability with significant CYP3A4 inhibition.

Cite this article as:

Hazra Abhijit, Mondal Chanchal, Chakraborty Debanjana, Halder K. Amit, Bharitkar P. Yogesh, Mondal K. Susanta, Banerjee Sukdeb, Jha Tarun and Mondal B. Nirup, Towards the Development of Anticancer Drugs from Andrographolide: Semisynthesis, Bioevaluation, QSAR Analysis and Pharmacokinetic Studies, Current Topics in Medicinal Chemistry 2015; 15 (11) . https://dx.doi.org/10.2174/1568026615666150317222706