Abstract
Background: Flavonolignans like silybin, hydnocarpin, and siliandrin are a group of natural compounds combining the structural moieties of flavonoid and phenylpropanoid (lignan). Hydnocarpin and silandrin have been less explored because of their trace occurrence in nature.
Objective: The present study aimed at chemical conversion of silybin to hydnocarpin and siliandrin. Another objective was to synthesize a series of amide derivatives and biologically evaluate them with regard to their anti-cancer effects.
Methods: In order to selectively convert silybin to 23-iodo silybin, 23-iodo hydnocarpin D and 23- iodo isosilandrin, the ratio of Ph3P, imidazole and molecular iodine was meticulously adjusted. These three iodide compounds were converted into amide compounds by chemical transformation. MTT method was applied to evaluate their anti-cancer potency. The binding affinity to related proteins was calculated by molecular docking.
Results: A total of 45 new amido-derivatives were synthesized and structurally characterized by NMR and HRMS. Some of them showed moderate to good antiproliferative potency against cancer cells. The activity of compound 10j was further testified by colony formation assay and molecular docking.
Conclusion: The synthesis of 23-iodo silybin, 23-iodo hydnocarpin D and 23-iodo isosilandrin from silybin was successfully accomplished by one simple iodination reaction. Some of the amide derivatives of sylibin/hydnocarpin D /silandrin exhibited a remarkable inhibitory effect of proliferation on cancer cells compared to silybin. These results would pave the way for further investigation on the derivatives of flavonolignans for the treatment of cancer.
Keywords: Hydnocarpin D, Silybin, Structural modification, Cytotoxicity, Flavonolignans, Flavonoids.
Current Topics in Medicinal Chemistry
Title:Structural Modification of Sylibin to Derivatives of Sylibin/Hydnocarpin D/Silandrin, and Evaluation of their Cytotoxicity against Cancer Cells
Volume: 21 Issue: 15
Author(s): Liwaliding Maihesuti , Hongwei Gao, Qi Wang, Jianguo Cao, Haji Akber Aisa*Guozheng Huang*
Affiliation:
- Key Laboratory of Plant Resources and Chemistry of Arid Zone, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, 830011,China
- Key Laboratory of Plant Resources and Chemistry of Arid Zone, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, 830011,China
Keywords: Hydnocarpin D, Silybin, Structural modification, Cytotoxicity, Flavonolignans, Flavonoids.
Abstract:
Background: Flavonolignans like silybin, hydnocarpin, and siliandrin are a group of natural compounds combining the structural moieties of flavonoid and phenylpropanoid (lignan). Hydnocarpin and silandrin have been less explored because of their trace occurrence in nature.
Objective: The present study aimed at chemical conversion of silybin to hydnocarpin and siliandrin. Another objective was to synthesize a series of amide derivatives and biologically evaluate them with regard to their anti-cancer effects.
Methods: In order to selectively convert silybin to 23-iodo silybin, 23-iodo hydnocarpin D and 23- iodo isosilandrin, the ratio of Ph3P, imidazole and molecular iodine was meticulously adjusted. These three iodide compounds were converted into amide compounds by chemical transformation. MTT method was applied to evaluate their anti-cancer potency. The binding affinity to related proteins was calculated by molecular docking.
Results: A total of 45 new amido-derivatives were synthesized and structurally characterized by NMR and HRMS. Some of them showed moderate to good antiproliferative potency against cancer cells. The activity of compound 10j was further testified by colony formation assay and molecular docking.
Conclusion: The synthesis of 23-iodo silybin, 23-iodo hydnocarpin D and 23-iodo isosilandrin from silybin was successfully accomplished by one simple iodination reaction. Some of the amide derivatives of sylibin/hydnocarpin D /silandrin exhibited a remarkable inhibitory effect of proliferation on cancer cells compared to silybin. These results would pave the way for further investigation on the derivatives of flavonolignans for the treatment of cancer.
Export Options
About this article
Cite this article as:
Maihesuti Liwaliding, Gao Hongwei , Wang Qi , Cao Jianguo , Aisa Akber Haji *, Huang Guozheng *, Structural Modification of Sylibin to Derivatives of Sylibin/Hydnocarpin D/Silandrin, and Evaluation of their Cytotoxicity against Cancer Cells, Current Topics in Medicinal Chemistry 2021; 21 (15) . https://dx.doi.org/10.2174/1568026621666210701142826
DOI https://dx.doi.org/10.2174/1568026621666210701142826 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Adaptogens—History and Future Perspectives
Adaptogens are pharmacologically active compounds or plant extracts that are associated with the ability to enhance the body’s stability against stress. The intake of adaptogens is associated not only with a better ability to adapt to stress and maintain or normalise metabolic functions but also with better mental and physical ...read more
AlphaFold in Medicinal Chemistry: Opportunities and Challenges
AlphaFold, a groundbreaking AI tool for protein structure prediction, is revolutionizing drug discovery. Its near-atomic accuracy unlocks new avenues for designing targeted drugs and performing efficient virtual screening. However, AlphaFold's static predictions lack the dynamic nature of proteins, crucial for understanding drug action. This is especially true for multi-domain proteins, ...read more
Artificial intelligence for Natural Products Discovery and Development
Our approach involves using computational methods to predict the potential therapeutic benefits of natural products by considering factors such as drug structure, targets, and interactions. We also employ multitarget analysis to understand the role of drug targets in disease pathways. We advocate for the use of artificial intelligence in predicting ...read more
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
- 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
-
MicroRNA in Cervical Carcinogenesis: Window of Therapeutic Potential
Current Women`s Health Reviews DFT and Molecular Docking Analysis of Newly Synthesized Compound (2E)-3-[3-(Benzyloxy) Phenyl]-1-(4’-Chlorophe-Nyl)- 2-Propen-1-One [Bpclpo]
Current Physical Chemistry Risk Factors for the Pap Test Cytological Changes in Iran: A Multicenter Case-Control Study
Current Women`s Health Reviews Interactions of Liposomes with Cells In Vitro and In Vivo: Opsonins and Receptors
Current Drug Metabolism Berberine Interfered with Breast Cancer Cells Metabolism, Balancing Energy Homeostasis
Anti-Cancer Agents in Medicinal Chemistry Chitosan and Quercetin: Potential Hand in Hand Encountering Tumors in Oral Delivery System
Current Pharmaceutical Design Approaches Targeting KV10.1 Open a Novel Window for Cancer Diagnosis and Therapy
Current Medicinal Chemistry Editorial: Parasite Polyamines
Current Pharmaceutical Design Feasibility of Margin Reduction for Level II and III Planning Target Volume in Head-and-Neck Image-Guided Radiotherapy – Dosimetric Assessment via A Deformable Image Registration Framework
Current Cancer Therapy Reviews Inflammation and Anemia
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Exploring the Bio-efficacies of Methanolic Extracts of Nostoc muscorum and Calothrix brevissima with their Characterization Using GC-MS
The Natural Products Journal Epigenetic control of cardiovascular health by nutritional polyphenols involves multiple chromatin-modifying writer-reader-eraser proteins
Current Topics in Medicinal Chemistry AMPK as a Potential Anticancer Target - Friend or Foe?
Current Pharmaceutical Design The Glutamate Hypothesis in ALS: Pathophysiology and Drug Development
Current Medicinal Chemistry CYP24A1 as a Potential Target for Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Antioxidant Properties of Fractions for Unripe Fruits of Capsicum annuum L. var. Conoides
Anti-Cancer Agents in Medicinal Chemistry Melanoma
Current Cancer Therapy Reviews E2F1 and NF-κB: Key Mediators of Inflammation-associated Cancers and Potential Therapeutic Targets
Current Cancer Drug Targets Lymphatic Targeting of Nanosystems for Anticancer Drug Therapy
Current Pharmaceutical Design Pathology Associated Memory Deficits in Swedish Mutant Genome-Based Amyloid Precursor Protein Transgenic Mice
Current Aging Science