Abstract
Abstract: Background: Alkynes are fundamental building blocks in synthetic chemistry with high pharmaceutical applications. Among the bioactive acetylenic molecules, propargylic alcohol is most important as almost all the marketed drugs contains quaternary centered propargylic alcohol functionality.
Objective: In this study we have synthesised and evaluated 3-hydroxy-3-ethynylindolin-2-one derivatives for in vitro cytotoxic activity.
Method: An expeditious method for direct alkynylation of isatins (ketones) has been developed using tetrabutylammonium fluoride (TBAF) as a catalyst in THF solvent at room temperature under metal-free conditions. Furthermore, this method is an economically viable process that also compliments green aspects like being a ligand/metal free process under ambient conditions. This reaction tolerated a wide range of substrates with good to excellent yields (80-94%).
Results: The results showed that the synthesized compounds (4m, 4n and 4p) has the ability to inhibit Akt kinase activity with IC50 values ranging from 7.7 to 9.8 µM.
Conclusion: All the 3-hydroxy-3-ethynylindolin-2-one derivatives were subjected for in vitro cytotoxic activity on five different cancer cell lines. Further, the synthesized compounds (4m, 4n and 4p) were evaluated for their ability to inhibit Akt kinase activity and exhibited good inhibition with IC50 values ranging from 7.7 to 9.8 µM..
Keywords: Alkynylation, oxindoles, TBAF, N-substituted isatins, Akt kinase activity, 3-hydroxy-3-ethynylindolin-2-one derivatives.
Anti-Cancer Agents in Medicinal Chemistry
Title:Synthesis and Bioevaluation of Quaternary Centered 3-hydroxy-3 (alkynyl)indolin-2-one Derivatives as Potential Cytotoxic Agents and Akt Kinase Inhibitors
Volume: 17 Issue: 14
Author(s): P. Sai Prathima*, R. Bikshapathi , Y. Poornachandra , V. Himabindu, G. Jagadeesh Kumar, N. Jagadeesh, C. Ganesh Kumar and V. Jayathirtha Rao*
Affiliation:
- Crop Protection Chemicals Division, CSIR-Indian Institute of Chemical Technology (IICT), Uppal Road, Tarnaka, Hyderabad, 500 607,India
- Crop Protection Chemicals Division, CSIR-Indian Institute of Chemical Technology (IICT), Uppal Road, Tarnaka, Hyderabad, 500 607,India
Keywords: Alkynylation, oxindoles, TBAF, N-substituted isatins, Akt kinase activity, 3-hydroxy-3-ethynylindolin-2-one derivatives.
Abstract: Abstract: Background: Alkynes are fundamental building blocks in synthetic chemistry with high pharmaceutical applications. Among the bioactive acetylenic molecules, propargylic alcohol is most important as almost all the marketed drugs contains quaternary centered propargylic alcohol functionality.
Objective: In this study we have synthesised and evaluated 3-hydroxy-3-ethynylindolin-2-one derivatives for in vitro cytotoxic activity.
Method: An expeditious method for direct alkynylation of isatins (ketones) has been developed using tetrabutylammonium fluoride (TBAF) as a catalyst in THF solvent at room temperature under metal-free conditions. Furthermore, this method is an economically viable process that also compliments green aspects like being a ligand/metal free process under ambient conditions. This reaction tolerated a wide range of substrates with good to excellent yields (80-94%).
Results: The results showed that the synthesized compounds (4m, 4n and 4p) has the ability to inhibit Akt kinase activity with IC50 values ranging from 7.7 to 9.8 µM.
Conclusion: All the 3-hydroxy-3-ethynylindolin-2-one derivatives were subjected for in vitro cytotoxic activity on five different cancer cell lines. Further, the synthesized compounds (4m, 4n and 4p) were evaluated for their ability to inhibit Akt kinase activity and exhibited good inhibition with IC50 values ranging from 7.7 to 9.8 µM..
Export Options
About this article
Cite this article as:
Prathima Sai P. *, Bikshapathi R., Poornachandra Y., Himabindu V. , Kumar Jagadeesh G. , Jagadeesh N. , Kumar Ganesh C. and Rao Jayathirtha V. *, Synthesis and Bioevaluation of Quaternary Centered 3-hydroxy-3 (alkynyl)indolin-2-one Derivatives as Potential Cytotoxic Agents and Akt Kinase Inhibitors, Anti-Cancer Agents in Medicinal Chemistry 2017; 17 (14) . https://dx.doi.org/10.2174/1871521409666170412125401
DOI https://dx.doi.org/10.2174/1871521409666170412125401 |
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
-
Peptide Nucleic Acids with a Structurally Biased Backbone. Updated Review and Emerging Challenges
Current Topics in Medicinal Chemistry Involvement of Potassium and Chloride Channels and Other Transporters in Volume Regulation by Spermatozoa
Current Pharmaceutical Design Direct Evidence on the Immune-Mediated Spontaneous Regression of Human Cancer: An Incentive for Pharmaceutical Companies to Develop a Novel Anti-Cancer Vaccine
Current Pharmaceutical Design Therapeutic Targets for the Management of Peripheral Nerve Injury- Induced Neuropathic Pain
CNS & Neurological Disorders - Drug Targets An Update on Developments in Female Hormonal Contraception
Current Women`s Health Reviews Retinoic Acid Metabolism and Mechanism of Action: A Review
Current Drug Metabolism New Direct and Frontal Tissue Acquisition Tools for Gene Expression Analysis in Personalized Medicine
Current Pharmacogenomics and Personalized Medicine Inflammation, Microenvironment, and the Immune System in Cancer Progression
Current Pharmaceutical Design Discovery of a Novel Anti-Cancer Agent Targeting Both Topoisomerase I & II as Well as Telomerase Activities in Human Lung Adenocarcinoma A549 Cells In Vitro and In Vivo: Cinnamomum verum Component Cuminaldehyde
Current Cancer Drug Targets Developments of Polo-like Kinase 1 (Plk1) Inhibitors as Anti-Cancer Agents
Mini-Reviews in Medicinal Chemistry Natural Compounds with Proteasome Inhibitory Activity for Cancer Prevention and Treatment
Current Protein & Peptide Science Synthetic and Natural Immunomodulators Acting as Interferon Inducers
Current Pharmaceutical Design Potential Therapeutic Targets of Curcumin, Most Abundant Active Compound of Turmeric Spice: Role in the Management of Various Types of Cancer
Recent Patents on Anti-Cancer Drug Discovery Adrenomedullin-RAMP2 System in Cardiovascular Development and Homeostasis
Current Hypertension Reviews Co-delivery of Plasmid DNA and Antisense Oligodeoxyribonucleotide into Human Carcinoma Cells by Cationic Liposomes
Current Pharmaceutical Biotechnology Biomarkers of Chronic Kidney Disease - Mineral and Bone Disorder (CKD-MBD), A Review of Published Patents and Patent Applications
Recent Patents on Biomarkers Application of Molecular Imaging Technologies in Antitumor Drug Development and Therapy
Current Pharmaceutical Design Mitochondrial DNA Mutations in Cancer: A Review
Current Topics in Medicinal Chemistry An Overview on the Development of New Potentially Active Camptothecin Analogs Against Cancer
Mini-Reviews in Medicinal Chemistry Lactate Transporters and pH Regulation: Potential Therapeutic Targets in Glioblastomas
Current Cancer Drug Targets