Abstract
Background: The anticancer properties of natural products calactin, calotropin and calotoxin are well established. However, the mechanisms of their action are unclear and the molecular targets pertinent to them are not detailed. In this study, potential anti-cancer targets of these compounds have been identified using reverse screening approaches that may provide valuable insights into anticancer drug development.
Objective: The aim of the study was to identify the potential anticancer targets of calactin, calotropin and calotoxin using reverse screening strategy.
Methods: The ligands were screened for potential targets based on their shape similarity and pharmacophore model matching. The overlapping targets obtained from both methods were verified using the reverse docking approach and validated by docking analysis. MM/PBSA calculation was performed to predict binding affinities between ligand and confirmed targets.
Results: Interleukin-2 inducible T cell kinase [ITK] was confirmed as a potential target of calactin (Ki= -10.3 kcal/mol), calotropin (Ki= -8.7 kcal/mol) and calotoxin (Ki= -10.2 kcal/mol). The ligands interacted with hinge region residues such as Met438 and Asp500 which occupy the highly conserved ATP binding site. Binding energies of calactin (ΔEbind = -29.18 kJ/mol), calotropin (-28.57 kJ/mol) and calotoxin (-21.21 kJ/mol) with ITK were higher than (more negative) positive control sunitinib (-15.03 kJ/mol) and standard staurosporine (-21.09 kJ/mol). Besides this, Interstitial collagenase [MMP1] was confirmed as a potential target of calotoxin (Ki= -8.2 kcal/mol). However the binding energy (ΔEbind = -11.89 kJ/mol) was lower compared to positive control batimastat (-21.07 kJ/mol).
Conclusion: The results of this study confirmed ITK as a potential target for calactin, calotropin and calotoxin. These compounds can therefore be used as lead molecules for the development of novel ITK inhibitors, which may have immense therapeutic applications as immune-suppressants and as anticancer drugs.
Keywords: Calactin, calotropin, calotoxin, interleukin-2 inducible T cell kinase [ITK], ITK inhibitors, reverse docking, anticancer, immune-suppressants.
Graphical Abstract
Current Drug Discovery Technologies
Title:Target Fishing of Calactin, Calotropin and Calotoxin Using Reverse Pharmacophore Screening and Consensus Inverse Docking Approach
Volume: 18 Issue: 6
Author(s): Vikram Parthasarathy, Achuthan Raghava Menon and Basavaraj Devaranavadagi*
Affiliation:
- Department of Biochemistry, Shri B.M. Patil Medical College, Hospital and Research Center, BLDE (Deemed to be University), Bangaramma Sajjan Campus, Sholapur Road, Vijayapura-586103, Karnataka,India
Keywords: Calactin, calotropin, calotoxin, interleukin-2 inducible T cell kinase [ITK], ITK inhibitors, reverse docking, anticancer, immune-suppressants.
Abstract: Background: The anticancer properties of natural products calactin, calotropin and calotoxin are well established. However, the mechanisms of their action are unclear and the molecular targets pertinent to them are not detailed. In this study, potential anti-cancer targets of these compounds have been identified using reverse screening approaches that may provide valuable insights into anticancer drug development.
Objective: The aim of the study was to identify the potential anticancer targets of calactin, calotropin and calotoxin using reverse screening strategy.
Methods: The ligands were screened for potential targets based on their shape similarity and pharmacophore model matching. The overlapping targets obtained from both methods were verified using the reverse docking approach and validated by docking analysis. MM/PBSA calculation was performed to predict binding affinities between ligand and confirmed targets.
Results: Interleukin-2 inducible T cell kinase [ITK] was confirmed as a potential target of calactin (Ki= -10.3 kcal/mol), calotropin (Ki= -8.7 kcal/mol) and calotoxin (Ki= -10.2 kcal/mol). The ligands interacted with hinge region residues such as Met438 and Asp500 which occupy the highly conserved ATP binding site. Binding energies of calactin (ΔEbind = -29.18 kJ/mol), calotropin (-28.57 kJ/mol) and calotoxin (-21.21 kJ/mol) with ITK were higher than (more negative) positive control sunitinib (-15.03 kJ/mol) and standard staurosporine (-21.09 kJ/mol). Besides this, Interstitial collagenase [MMP1] was confirmed as a potential target of calotoxin (Ki= -8.2 kcal/mol). However the binding energy (ΔEbind = -11.89 kJ/mol) was lower compared to positive control batimastat (-21.07 kJ/mol).
Conclusion: The results of this study confirmed ITK as a potential target for calactin, calotropin and calotoxin. These compounds can therefore be used as lead molecules for the development of novel ITK inhibitors, which may have immense therapeutic applications as immune-suppressants and as anticancer drugs.
Export Options
About this article
Cite this article as:
Parthasarathy Vikram , Menon Raghava Achuthan and Devaranavadagi Basavaraj *, Target Fishing of Calactin, Calotropin and Calotoxin Using Reverse Pharmacophore Screening and Consensus Inverse Docking Approach, Current Drug Discovery Technologies 2021; 18 (6) : e130921188782 . https://dx.doi.org/10.2174/1570163817666201207143958
DOI https://dx.doi.org/10.2174/1570163817666201207143958 |
Print ISSN 1570-1638 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6220 |
Related Books
![](/images/wayfinder.jpg)
- Author Guidelines
- Bentham Author Support Services (BASS)
- 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
-
Statins: A Conceivable Remedial Role for the Regulation of Cancer Progression
Current Cancer Therapy Reviews Titanocenes as Anticancer Agents: Recent Insights
Medicinal Chemistry Candidiasis: A Fungal Infection- Current Challenges and Progress in Prevention and Treatment
Infectious Disorders - Drug Targets Anti-Epidermal Growth Factor Receptor Antibodies in the Treatment of Metastatic Colorectal Cancer
Recent Patents on Anti-Cancer Drug Discovery The Role of cMet in Non-Small Cell Lung Cancer Resistant to EGFRInhibitors: Did We Really Find the Target?
Current Drug Targets Prevention of Cancer in the Upper Gastrointestinal Tract with COX-Inhibition. Still an Option?
Current Pharmaceutical Design Green Tea Catechins as Novel Antitumor and Antiangiogenic Compounds
Current Medicinal Chemistry - Anti-Cancer Agents Recent Progress in the Pharmacology of Imidazo[1,2-a]pyridines
Mini-Reviews in Medicinal Chemistry Recent Patents, Formulation and Characterization of Nanoliposomes
Recent Patents on Drug Delivery & Formulation MicroRNAs as Cancer Biomarkers
MicroRNA Systemic Sclerosis: Clinical Manifestations
Current Rheumatology Reviews The Role of Transesophageal Echocardiography in the Intraoperative Period
Current Cardiology Reviews Paeonol Inhibits Migration, Invasion and Bone Adhesion of Small Cell Lung Cancer Cells
Current Signal Transduction Therapy An Overview of Innovations in Analysis and Beneficial Health Effects of Wine Polyphenols
Mini-Reviews in Medicinal Chemistry Phenolic Compounds as Antioxidants: Carbonic Anhydrase Isoenzymes Inhibitors
Mini-Reviews in Medicinal Chemistry Prevention of Upper Gastrointestinal Ulcer and Complications in Low-Dose Aspirin Users
Current Pharmaceutical Design Epigenetic Regulation of Cytochrome P450 Enzymes and Clinical Implication
Current Drug Metabolism Mucoadhesive Polymeric Platform for Drug Delivery; A Comprehensive Review
Current Drug Delivery Structure-Activity Relationship Analyses of Glycyrrhetinic Acid Derivatives as Anticancer Agents
Mini-Reviews in Medicinal Chemistry The Inhibition of Cell Proliferation Using Silencing of N-Cadherin Gene by siRNA Process in Human Melanoma Cell Lines
Current Medicinal Chemistry