Abstract
Background: Phosphatidylinositol-3-kinase α (PI3Kα) is a ubiquitous intracellular enzyme, mainly involved in intracellular signaling pathways, promotes cellular growth, proliferation, and differentiation. Therefore, inhibition of PI3K can be a hotspot in molecular targeted therapy for the treatment of cancer.
Methods: The present research work involves molecular docking studies performed to screen derivatives of urea and thiourea bearing thieno [3,2-d]-pyrimidines against the active site of PI3K enzyme using MOE.2008.10. The designed structures (6a-f) and (7a-j) were synthesized by the facile synthetic methods and evaluated for their anticancer activity against HT-29 and MCF-7 cell lines and inhibitory activity against PI3Kα enzyme.
Results: Among the tested compounds, 4-(4-(2-(3-(pyrimidin-2-yl)thioureido)ethyl)piperazin-1-yl)thieno[3,2- d]pyrimidine-6-carboxamide (7f) showed the highest anticancer activity against HT-29 and MCF-7 cell lines with IC50 values of 2.18 µM and 4.25 µM, respectively. Further, the same compound also exhibited potent PI3Kα inhibitory activity with IC50 value of 1.26 µM.
Conclusion: Docking studies supported the initial pharmacophoric hypothesis and suggested a mode of interaction at the active binding site of PI3Kα, demonstrating that the target compounds were potential inhibitory agents for cancer therapy.
Keywords: Thieno [3, 2-d]-pyrimidines, anticancer agents, molecular docking, PI3K inhibitors, novel urea, facile synthetic methods.
Anti-Cancer Agents in Medicinal Chemistry
Title:Design, Synthesis and Biological Evaluation of Novel Urea and Thiourea Bearing thieno[3,2-d]-pyrimidines as PI3 Kinase Inhibitors
Volume: 18 Issue: 6
Author(s): Srinu Bodige, Parameshwar Ravula, Kali Charan Gulipalli, Srinivas Endoori, J.N. Narendra Sharath Chandra, Purna Koteswara Rao Cherukumalli, Vanaja.G.R and Nareshvarma Seelam*
Affiliation:
- Department of Chemistry, Koneru Lakshmaiah Education Foundation, Green Fields, Vaddeswaram, Guntur, 522502,India
Keywords: Thieno [3, 2-d]-pyrimidines, anticancer agents, molecular docking, PI3K inhibitors, novel urea, facile synthetic methods.
Abstract: Background: Phosphatidylinositol-3-kinase α (PI3Kα) is a ubiquitous intracellular enzyme, mainly involved in intracellular signaling pathways, promotes cellular growth, proliferation, and differentiation. Therefore, inhibition of PI3K can be a hotspot in molecular targeted therapy for the treatment of cancer.
Methods: The present research work involves molecular docking studies performed to screen derivatives of urea and thiourea bearing thieno [3,2-d]-pyrimidines against the active site of PI3K enzyme using MOE.2008.10. The designed structures (6a-f) and (7a-j) were synthesized by the facile synthetic methods and evaluated for their anticancer activity against HT-29 and MCF-7 cell lines and inhibitory activity against PI3Kα enzyme.
Results: Among the tested compounds, 4-(4-(2-(3-(pyrimidin-2-yl)thioureido)ethyl)piperazin-1-yl)thieno[3,2- d]pyrimidine-6-carboxamide (7f) showed the highest anticancer activity against HT-29 and MCF-7 cell lines with IC50 values of 2.18 µM and 4.25 µM, respectively. Further, the same compound also exhibited potent PI3Kα inhibitory activity with IC50 value of 1.26 µM.
Conclusion: Docking studies supported the initial pharmacophoric hypothesis and suggested a mode of interaction at the active binding site of PI3Kα, demonstrating that the target compounds were potential inhibitory agents for cancer therapy.
Export Options
About this article
Cite this article as:
Bodige Srinu , Ravula Parameshwar , Gulipalli Charan Kali , Endoori Srinivas, Chandra Narendra Sharath J.N., Cherukumalli Koteswara Rao Purna , Vanaja.G.R and Seelam Nareshvarma*, Design, Synthesis and Biological Evaluation of Novel Urea and Thiourea Bearing thieno[3,2-d]-pyrimidines as PI3 Kinase Inhibitors, Anti-Cancer Agents in Medicinal Chemistry 2018; 18 (6) . https://dx.doi.org/10.2174/1871520618666180209151018
DOI https://dx.doi.org/10.2174/1871520618666180209151018 |
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
-
Microenvironmental Regulation of Cancer Stem Cell Phenotypes
Current Stem Cell Research & Therapy From ImmunoToxins to ImmunoRNases
Current Pharmaceutical Biotechnology Cytotoxic Anticancer Candidates from Terrestrial Plants
Anti-Cancer Agents in Medicinal Chemistry Dermatological, Cardiovascular and Neurological Morphohistopathological Effects of Fluoropyrimidine-based Chemotherapy in Humans
Clinical Cancer Drugs Preoperative Pulmonary Assessment: A Review
Current Respiratory Medicine Reviews Understanding XPO1 Target Networks Using Systems Biology and Mathematical Modeling
Current Pharmaceutical Design Proinflammatory Cytokines in Breast Cancer: Mechanisms of Action and Potential Targets for Therapeutics
Current Drug Targets Biologics for ANCA-Associated Vasculitis
Inflammation & Allergy - Drug Targets (Discontinued) Editorial from Editor-in-Chief
Current Medical Imaging Role of Gap Junction Channel in the Development of Beat-to-Beat Action Potential Repolarization Variability and Arrhythmias
Current Pharmaceutical Design Choline Kinase: An Important Target for Cancer
Current Medicinal Chemistry Irradiation Toxicity and Inflammatory Bowel Diseases (IBD): Review
Reviews on Recent Clinical Trials Atrial Natriuretic Peptide: A Magic Bullet for Cancer Therapy Targeting Wnt Signaling and Cellular pH Regulators
Current Medicinal Chemistry Inhibition of TGF-β Signaling in Tumor Cells by Small Molecule Src Family Kinase Inhibitors
Anti-Cancer Agents in Medicinal Chemistry Pathophysiology of Metastatic Bone Disease and the Role of the Second Generation of Bisphosphonates: From Basic Science to Medicine
Current Pharmaceutical Design Evidence for Epigenetic Alterations in Turner Syndrome Opens up Feasibility of New Pharmaceutical Interventions
Current Pharmaceutical Design The Imaging of Apoptosis with the Radiolabelled Annexin A5: A New Tool in Translational Research
Current Clinical Pharmacology Management of Early Stage Cervical Cancer
Reviews on Recent Clinical Trials “What Is And What Should Never Be”<sup>#</sup>: Use and Misuse of HPV Testing in Cervical Cancer Prevention Strategies
Current Women`s Health Reviews The Mevalonate Pathway and Innate Immune Hyper-Responsiveness in the Pathogenesis of COPD and Lung Cancer: Potential for Chemoprevention
Current Molecular Pharmacology