Abstract
Syringic acid, a known plant phenolic compound and its analogues are known to possess high proteasome inhibitory activity. In the current work, we describe synthesis, characterization, DFT, docking of syringic acid (SA) and analogues (SAA1 and SAA2) and biological effects were studied. Syringic acid and its analogues were docked for the first time with the crystal structures of β5 proteasome of diverse eukaryotic organisms. Among all proteasomes, the humanoid proteasome showed the highest degree of docking conformation and low inhibition constant (Ki). SAA2 specifically displayed binding to the N-terminal Thr1 residue in the S1 pocket of Mus musculus β5 proteasome along with threonine, lysine and arginine; conventionally involved major amino acid residues in ligand binding. The geometrical properties (B3LYP/6- 31g (d, p)) and electrostatic potentials of molecules were computed using DFT calculations. A detailed molecular picture of the compounds and its interactions was obtained from NBO analysis. SA-analogues elucidated potent antioxidant activities and good antibacterial activity. In-vitro DNA binding studies revealed that all molecules had strong binding at the major groove of dsDNA. In the view of medical applicability, proteasome inhibition is an important therapeutic strategy for various types of cancers. Therefore, current discoveries may encourage the rational design and development of new chemical entities of syringic acid based chemotherapeutics.
Keywords: β5 proteasome, DFT-density functional theory, multiple myeloma, tetramethylsilane, ubiquitin-proteasome pathway.
Anti-Cancer Agents in Medicinal Chemistry
Title:Exploring the Binding Affinity of Novel Syringic Acid Analogues and Critical Determinants of Selectivity as Potent Proteasome Inhibitors
Volume: 16 Issue: 11
Author(s): Srinivasulu Cheemanapalli, C. M. Anuradha, P. Madhusudhana, M. Mahesh, Pongali B. Raghavendra and Chitta S. Kumar
Affiliation:
Keywords: β5 proteasome, DFT-density functional theory, multiple myeloma, tetramethylsilane, ubiquitin-proteasome pathway.
Abstract: Syringic acid, a known plant phenolic compound and its analogues are known to possess high proteasome inhibitory activity. In the current work, we describe synthesis, characterization, DFT, docking of syringic acid (SA) and analogues (SAA1 and SAA2) and biological effects were studied. Syringic acid and its analogues were docked for the first time with the crystal structures of β5 proteasome of diverse eukaryotic organisms. Among all proteasomes, the humanoid proteasome showed the highest degree of docking conformation and low inhibition constant (Ki). SAA2 specifically displayed binding to the N-terminal Thr1 residue in the S1 pocket of Mus musculus β5 proteasome along with threonine, lysine and arginine; conventionally involved major amino acid residues in ligand binding. The geometrical properties (B3LYP/6- 31g (d, p)) and electrostatic potentials of molecules were computed using DFT calculations. A detailed molecular picture of the compounds and its interactions was obtained from NBO analysis. SA-analogues elucidated potent antioxidant activities and good antibacterial activity. In-vitro DNA binding studies revealed that all molecules had strong binding at the major groove of dsDNA. In the view of medical applicability, proteasome inhibition is an important therapeutic strategy for various types of cancers. Therefore, current discoveries may encourage the rational design and development of new chemical entities of syringic acid based chemotherapeutics.
Export Options
About this article
Cite this article as:
Cheemanapalli Srinivasulu, Anuradha M. C., Madhusudhana P., Mahesh M., Raghavendra B. Pongali and Kumar S. Chitta, Exploring the Binding Affinity of Novel Syringic Acid Analogues and Critical Determinants of Selectivity as Potent Proteasome Inhibitors, Anti-Cancer Agents in Medicinal Chemistry 2016; 16 (11) . https://dx.doi.org/10.2174/1871520616666160513131928
DOI https://dx.doi.org/10.2174/1871520616666160513131928 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...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
Related Articles
-
The Gut Microbiota as a Target for Improved Surgical Outcome and Improved Patient Care
Current Pharmaceutical Design Anti-Inflammatory Effects of Triterpenoids; Naturally Occurring and Synthetic Agents
Mini-Reviews in Organic Chemistry Reversal in Cognition Impairments, Cholinergic Dysfunction, and Cerebral Oxidative Stress Through the Modulation of Ryanodine Receptors (RyRs) and Cysteinyl Leukotriene-1 (CysLT1) Receptors
Current Neurovascular Research The Proteasome in Health and Disease
Current Pharmaceutical Design TNF-α/Cycloheximide-Induced Oxidative Stress and Apoptosis in Murine Intestinal Epithelial MODE-K Cells
Current Pharmaceutical Design Encephalopathy: A Vicious Cascade Following Forebrain Ischemia and Hypoxia
Central Nervous System Agents in Medicinal Chemistry Modulation of Cardiovascular Remodeling with Statins: Fact or Fiction?
Current Vascular Pharmacology Recent Insights into the Role of Prostanoids in Atherosclerotic Vascular Disease
Current Vascular Pharmacology Systemic Sclerosis-Related Pulmonary Hypertension: Unique Characteristics and Future Treatment Targets
Current Pharmaceutical Design Diabetic Cardiomyopathy and its Prevention by Metallothionein: Experimental Evidence, Possible Mechanisms and Clinical Implications
Current Medicinal Chemistry Protective Effect of Notoginsenoside R1 on an APP/PS1 Mouse Model of Alzheimer's Disease by Up-Regulating Insulin Degrading Enzyme and Inhibiting Aβ Accumulation
CNS & Neurological Disorders - Drug Targets HSP27 Protects the Blood-Brain Barrier Against Ischemia-Induced Loss of Integrity
CNS & Neurological Disorders - Drug Targets Melatonin and Respiratory Diseases: A Review
Current Topics in Medicinal Chemistry Improved Anti-inflammatory Activity and Potential Cytoprotective Properties of Tolfenamic Acid, Naproxen and Indomethacin Derivatives
Letters in Drug Design & Discovery Cardioprotection by Targeting the Pool of Resident and Extracardiac Progenitors
Current Drug Targets 20-Hydroxyeicosatetraenoic Acid is a Potential Therapeutic Target in Cardiovascular Diseases
Current Drug Metabolism Therapeutic Potential of Natural Products from Terrestrial Plants as TNF-α Antagonist
Current Topics in Medicinal Chemistry Novel Drug Targets for the Treatment of Cardiac Diseases
Current Pharmacogenomics and Personalized Medicine Mitochondria as Therapeutic Targets of Estrogen Action in the Central Nervous System
Current Drug Targets - CNS & Neurological Disorders AMPK in Neurodegenerative Diseases: Implications and Therapeutic Perspectives
Current Drug Targets