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.
Keywords: 1, 3-dipolar cycloaddition, 2D and 3D QSAR, Andrographolide, Anticancer, Dispiro-pyrrolidino/ pyrrolizidinooxindole, Pharmacokinetics.
Current Topics in Medicinal Chemistry
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.
Export Options
About this article
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
DOI https://dx.doi.org/10.2174/1568026615666150317222706 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Intravenous Immunoglobulin as a Potential Therapy for Refractory Urticaria - A Review
Inflammation & Allergy - Drug Targets (Discontinued) New Antipsychotics and Schizophrenia: A Review on Efficacy and Side Effects
Current Medicinal Chemistry Thoracic Surgical Approaches in the Trauma Setting: A Basic Review
Current Respiratory Medicine Reviews Regulation of Ingestive Behavior, the Upper Gastrointestinal Motility and Gastric Acid Secretion by Ghrelin in Mammals
Current Nutrition & Food Science Studies on Novel Pyridine and 2-pyridone Derivatives of N-arylpiperazine as α-adrenoceptor Ligands
Medicinal Chemistry ATP-Sensitive Potassium Channels
Current Pharmaceutical Design Therapeutic Interventions in the Glyc(oxid)ation Pathway
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Modulation of Ischemic Brain Injury and Neuroinflammation by Adenosine A2A Receptors
Current Pharmaceutical Design Molecular Basis of Mineralocorticoid Receptor Action in the Nervous System
CNS & Neurological Disorders - Drug Targets Oligonucleotide-Based Molecular Therapy for Restenosis after Angioplasty
Current Drug Targets Recent Applications of Doebner, Doebner-von Miller and Knoevenagel-Doebner Reactions in Organic Syntheses
Current Organic Synthesis The Nitric Oxide Prodrug JS-K and Its Structural Analogues as Cancer Therapeutic Agents
Anti-Cancer Agents in Medicinal Chemistry A Dig Deep to Scout the Pharmacological and Clinical Facet of Garlic (<i>Allium sativum</i>)
Current Traditional Medicine New Antipsychotics in Treatment of Mood Instability and Cognitive Perceptual Symptoms in Borderline Personality Disorder
Current Psychopharmacology Diabetes and Its Complications: Therapies Available, Anticipated and Aspired
Current Diabetes Reviews Cyclopentenone Prostaglandins as Anti-Inflammatory Agents: A Novel Therapeutic Strategy?
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Progress in Syntheses of 3-n-Butylphthalide and Its Analogues
Current Organic Chemistry The Role of Growth Factors in the Prevention and Treatment of Chemotherapy-Induced Peripheral Neurotoxicity
Current Drug Safety Synthesis and Study the Antimicrobial Activity of Novel 2-(1H-indol-3-yl)- N-(3, 4-diphenylthiazol-2(3H)-ylidene) Ethanamine Derivatives
Medicinal Chemistry Biochemical Properties of Peptides Encrypted in Bovine Milk Proteins
Current Medicinal Chemistry