Abstract
Background: For further exploration of the promising pyrrolizine scaffold and in continuation of our previous work, that proved the potential anticancer activity of the hit compound I, a new series of pyrrolizines 2-5 and 7-9 were designed and synthesized.
Methods: Structures of the new compounds were confirmed by IR, 1H-NMR, 13C-NMR and elemental analysis. Antitumor activity for the prepared compounds against human breast adenocarcinoma (MCF-7), liver (HEPG2) and colon (HCT116) cancer cell lines was evaluated using SRB assay method.
Result: Compounds 2, 3 and 5 were the most potent on colon cancer cells, their IC50 values were less than 5 µM. Compounds 2, 3 and 8 were the most potent on liver cancer cells, their IC50 values were less than 10 µM. As for MCF7, compounds 2, 7, 8 and 9 were the most active with IC50 values less than 10 µM. We can conclude that combining pyrrolizine scaffold with urea gave abroad spectrum anticancer agent 2 against the three tested cell lines. Micronucleus assays showed that compounds 2, 3, 8 are mutagenic and can induce apoptosis. In addition, caspase-3 activation was evaluated and compound 2 showed increase in the level of caspase-3 (9 folds) followed by 3 (8.28 folds) then 8 (7.89 folds).
Conclusion: The obtained results encourage considering these three compounds as novel anticancer prototypes.
Keywords: Pyrrolizine, uridopyrrolizine, pyrimidopyrrolizine, anticancer, caspase-3, micronucleus.
Anti-Cancer Agents in Medicinal Chemistry
Title:Pyrrolizines as Potential Anticancer Agents: Design, Synthesis, Caspase-3 activation and Micronucleus (MN) Induction
Volume: 18 Issue: 15
Author(s): Amany Belal*
Affiliation:
- Pharmaceutical Chemistry Department, College of Pharmacy, Taif University, Taif 21974,Saudi Arabia
Keywords: Pyrrolizine, uridopyrrolizine, pyrimidopyrrolizine, anticancer, caspase-3, micronucleus.
Abstract: Background: For further exploration of the promising pyrrolizine scaffold and in continuation of our previous work, that proved the potential anticancer activity of the hit compound I, a new series of pyrrolizines 2-5 and 7-9 were designed and synthesized.
Methods: Structures of the new compounds were confirmed by IR, 1H-NMR, 13C-NMR and elemental analysis. Antitumor activity for the prepared compounds against human breast adenocarcinoma (MCF-7), liver (HEPG2) and colon (HCT116) cancer cell lines was evaluated using SRB assay method.
Result: Compounds 2, 3 and 5 were the most potent on colon cancer cells, their IC50 values were less than 5 µM. Compounds 2, 3 and 8 were the most potent on liver cancer cells, their IC50 values were less than 10 µM. As for MCF7, compounds 2, 7, 8 and 9 were the most active with IC50 values less than 10 µM. We can conclude that combining pyrrolizine scaffold with urea gave abroad spectrum anticancer agent 2 against the three tested cell lines. Micronucleus assays showed that compounds 2, 3, 8 are mutagenic and can induce apoptosis. In addition, caspase-3 activation was evaluated and compound 2 showed increase in the level of caspase-3 (9 folds) followed by 3 (8.28 folds) then 8 (7.89 folds).
Conclusion: The obtained results encourage considering these three compounds as novel anticancer prototypes.
Export Options
About this article
Cite this article as:
Belal Amany*, Pyrrolizines as Potential Anticancer Agents: Design, Synthesis, Caspase-3 activation and Micronucleus (MN) Induction, Anti-Cancer Agents in Medicinal Chemistry 2018; 18 (15) . https://dx.doi.org/10.2174/1871520618666180409155520
DOI https://dx.doi.org/10.2174/1871520618666180409155520 |
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
-
Targeting Tumor Lymphangiogenesis: An Update
Current Medicinal Chemistry Treatment of Diffuse-Type Gastric Cancer Cells Using 213Bi-Radioimmunoconjugates In Vitro and In Vivo Following Intraperitoneal Dissemination
Current Radiopharmaceuticals MicroRNAs as Potential Diagnostic and Prognostic Biomarkers in Hepatocellular Carcinoma
Current Drug Targets Patent Selections
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Stem Cell Guardians – Old and New Perspectives in LSC Biology
Current Drug Targets Lipid-based Nano-phytomedicines for Disease Treatment and Theranostic Applications
Current Nanomedicine Bortezomib and Arsenious Acid Synergistically Inhibit HL-60 Cells Viability in vitro and in vivo
Current Signal Transduction Therapy The Role of 3D Pharmacophore Mapping Based Virtual Screening for Identification of Novel Anticancer Agents: An Overview
Current Topics in Medicinal Chemistry Inhibition of RET Activated Pathways: Novel Strategies for Therapeutic Intervention in Human Cancers
Current Pharmaceutical Design Malignant Mesothelioma Resistance to Apoptosis: Recent Discoveries and their Implication for Effective Therapeutic Strategies
Current Medicinal Chemistry Reversing Breast Cancer Stem Cell into Breast Somatic Stem Cell
Current Pharmaceutical Biotechnology Immune Response Manipulation: Recombinant Immunoreceptors Endow T-Cells with Predefined Specificity
Current Pharmaceutical Design Liposomes as Versatile Platform for Cancer Theranostics: Therapy, Bio-imaging, and Toxicological Aspects
Current Pharmaceutical Design Tissue Elasticity Bridges Cancer Stem Cells to the Tumor Microenvironment Through microRNAs: Implications for a “Watch-and-Wait” Approach to Cancer
Current Stem Cell Research & Therapy Personalized Medicine in Oncology: A Personal View with Myths and Facts
Current Clinical Pharmacology Current Development of ROS-Modulating Agents as Novel Antitumor Therapy
Current Cancer Drug Targets Identification of Novel Small-Molecule ASGP-R Ligands
Current Drug Delivery The Development of MetAP-2 Inhibitors in Cancer Treatment
Current Medicinal Chemistry Editorial (Thematic Issue: Gene Therapy for Gastrointestinal and Liver Cancers: Past Experience, Current Status and Future Perspectives)
Current Gene Therapy IAPs as a Target for Anticancer Therapy
Current Cancer Drug Targets