Abstract
Aim and Objective: Cancer has become one of the leading causes of morbidity and mortality worldwide. Limitations associated with existing agents increase the need to develop more effective anticancer drugs to improve the therapeutic arsenal available. The aim of this study was to synthesize and evaluate the antiproliferative effects of three new thiazacridine derivatives.
Material and Methods: Using a three steps synthesis reaction, three novel thiazacridine derivatives were obtained and characterized: (Z)-5-acridin-9-ylmethylene-3-(4-methyl-benzyl)-4-thioxo-thiazolidin- 2-one (LPSF/AC-99), (Z)-5-acridin-9-ylmethylene-3-(4-chloro-benzyl)-4-thioxo-thiazolidin-2- one (LPSF/AC-119) and (Z)-5-acridin-9-ylmethylene-3-(3-chloro-benzyl)-4-thioxo-thiazolidin-2- one (LPSF/AC-129). Toxicity and selectivity assays were performed by colorimetric assay. Then, changes in cell cycle and cell death induction mechanisms were assessed by flow cytometry.
Results: All compounds exhibited cytotoxicity to Raji (Burkitt's lymphoma) and Jurkat (acute T cell leukemia) cells, where LPSF/AC-119 showed best IC50 values (0.6 and 1.53 µ M, respectively). LPSF/AC-129 was the only cytotoxic compound in glioblastoma cell line NG97 (IC50 = 55.77 µ M). None of the compounds were toxic to normal human cells and induced neoplastic cell death primarily by apoptosis.
Conclusion: All derivatives were more cytotoxic to hematopoietic neoplastic cells when compared to solid tumor derived cells. All three compounds are promising for in vivo and combination therapy studies against cancer.
Keywords: Cancer, hematopoietic neoplastic cells, acridine, therapeutic innovation, cytotoxicity, apoptosis.
Combinatorial Chemistry & High Throughput Screening
Title:Synthesis and Anticancer Evaluation of Thiazacridine Derivatives Reveals New Selective Molecules to Hematopoietic Neoplastic Cells
Volume: 20 Issue: 8
Author(s): Moacyr J.B. de Melo Rego*, Wanessa l.b. de Sena, Ricardo O. de Moura, Iris T.T. Jacob, Thiago U. Lins e Lins, Michelly C. Pereira, Maria do Carmo A. Lima, Marina R. Galdino-Pitta, Ivan da R. Pitta and Maira G. da Rocha Pitta
Affiliation:
- Department of Biochemistry, Federal University of Pernambuco, Laboratory of Immunomodulation and New Therapeutic Approaches (LINAT), Recife,Brazil
Keywords: Cancer, hematopoietic neoplastic cells, acridine, therapeutic innovation, cytotoxicity, apoptosis.
Abstract: Aim and Objective: Cancer has become one of the leading causes of morbidity and mortality worldwide. Limitations associated with existing agents increase the need to develop more effective anticancer drugs to improve the therapeutic arsenal available. The aim of this study was to synthesize and evaluate the antiproliferative effects of three new thiazacridine derivatives.
Material and Methods: Using a three steps synthesis reaction, three novel thiazacridine derivatives were obtained and characterized: (Z)-5-acridin-9-ylmethylene-3-(4-methyl-benzyl)-4-thioxo-thiazolidin- 2-one (LPSF/AC-99), (Z)-5-acridin-9-ylmethylene-3-(4-chloro-benzyl)-4-thioxo-thiazolidin-2- one (LPSF/AC-119) and (Z)-5-acridin-9-ylmethylene-3-(3-chloro-benzyl)-4-thioxo-thiazolidin-2- one (LPSF/AC-129). Toxicity and selectivity assays were performed by colorimetric assay. Then, changes in cell cycle and cell death induction mechanisms were assessed by flow cytometry.
Results: All compounds exhibited cytotoxicity to Raji (Burkitt's lymphoma) and Jurkat (acute T cell leukemia) cells, where LPSF/AC-119 showed best IC50 values (0.6 and 1.53 µ M, respectively). LPSF/AC-129 was the only cytotoxic compound in glioblastoma cell line NG97 (IC50 = 55.77 µ M). None of the compounds were toxic to normal human cells and induced neoplastic cell death primarily by apoptosis.
Conclusion: All derivatives were more cytotoxic to hematopoietic neoplastic cells when compared to solid tumor derived cells. All three compounds are promising for in vivo and combination therapy studies against cancer.
Export Options
About this article
Cite this article as:
de Melo Rego J.B. Moacyr*, de Sena l.b. Wanessa , de Moura O. Ricardo , Jacob T.T. Iris , Lins e Lins U. Thiago, Pereira C. Michelly , do Carmo A. Lima Maria , Galdino-Pitta R. Marina , da R. Pitta Ivan and da Rocha Pitta G. Maira , Synthesis and Anticancer Evaluation of Thiazacridine Derivatives Reveals New Selective Molecules to Hematopoietic Neoplastic Cells, Combinatorial Chemistry & High Throughput Screening 2017; 20 (8) . https://dx.doi.org/10.2174/1386207320666170724114802
DOI https://dx.doi.org/10.2174/1386207320666170724114802 |
Print ISSN 1386-2073 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5402 |
Call for Papers in Thematic Issues
Artificial Intelligence Methods for Biomedical, Biochemical and Bioinformatics Problems
Recently, a large number of technologies based on artificial intelligence have been developed and applied to solve a diverse range of problems in the areas of biomedical, biochemical and bioinformatics problems. By utilizing powerful computing resources and massive amounts of data, methods based on artificial intelligence can significantly improve the ...read more
Emerging trends in diseases mechanisms, noble drug targets and therapeutic strategies: focus on immunological and inflammatory disorders
Recently infectious and inflammatory diseases have been a key concern worldwide due to tremendous morbidity and mortality world Wide. Recent, nCOVID-9 pandemic is a good example for the emerging infectious disease outbreak. The world is facing many emerging and re-emerging diseases out breaks at present however, there is huge lack ...read more
Exploring Spectral Graph Theory in Combinatorial Chemistry
Scope of the Thematic Issue: Combinatorial chemistry involves the synthesis and analysis of a large number of diverse compounds simultaneously. Traditional methods rely on brute force experimentation, which can be time-consuming and resource-intensive. Spectral Graph Theory, a branch of mathematics dealing with the properties of graphs in relation to the ...read more
Integrating Network Pharmacology and Traditional Medicine: A New Perspective in Drug Mechanism Research
Network pharmacology is a network construction and network topology analysis strategy that combines pharmacology and pharmacodynamics. In recent years, network pharmacology has emerged as a powerful tool that can be integrated with pharmacology. Natural products commonly function in multicomponent, multitarget, and multipathway systems. Some examples encompass Ayurveda, traditional Chinese medicines ...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
-
Toll-like Receptors as a Novel Therapeutic Target for Natural Products Against Chronic Diseases
Current Drug Targets Resveratrol, a Phytochemical Inducer of Multiple Cell Death Pathways: Apoptosis, Autophagy and Mitotic Catastrophe
Current Medicinal Chemistry Inflammatory Bowel Disease: Etiology, Pathogenesis and Current Therapy
Current Pharmaceutical Design Experimental Strategies in Autoimmunity: Antagonists of Cytokines and their Receptors, Nanocarriers, Inhibitors of Immunoproteasome, Leukocyte Migration and Protein Kinases
Current Pharmaceutical Design Anti-MDR Effects of Quercetin and its Nanoemulsion in Multidrug-Resistant Human Leukemia Cells
Anti-Cancer Agents in Medicinal Chemistry The Development of Copper Radiopharmaceuticals for Imaging and Therapy
Medicinal Chemistry Progress in Multiple Sclerosis Genetics
Current Genomics Chemoradiotherapy of Human Tumors: Novel Approaches from Nanomedicine
Current Pharmaceutical Design Embryonic Stem Cell MicroRNAs: Defining Factors in Induced Pluripotent (iPS) and Cancer (CSC) Stem Cells?
Current Stem Cell Research & Therapy Targeting Molecular Imaging of Breast Cancer by Radioimmunodetection Method in Nuclear Medicine
Current Molecular Imaging (Discontinued) Biomarkers for VEGF-Targeted Therapy in Renal Cell Carcinoma: Critical Review of Level of Evidence and Up to Date
Recent Patents on Biomarkers mTOR Inhibition and the Tumor Vasculature
Current Angiogenesis (Discontinued) Recent Patents on Mesenchymal Stem Cell Mediated Therapy in Inflammatory Diseases
Recent Patents on Inflammation & Allergy Drug Discovery Senescence and Cell Death Pathways and Their Role in Cancer Therapeutic Outcome
Current Medicinal Chemistry Progress in the Development of Bestatin Analogues as Aminopeptidases Inhibitors
Current Medicinal Chemistry Strategies for Increasing the Solubility and Bioavailability of Anticancer Compounds: β-Lapachone and Other Naphthoquinones
Current Pharmaceutical Design Thiopurine Immunomodulators in Ulcerative Colitis: Moving Forward with Current Evidence
Current Drug Targets Mammary Development and Breast Cancer: The Role of Stem Cells
Current Molecular Medicine Design, Synthesis and Biological Evaluation of a Phenyl Butyric Acid Derivative, N-(4-chlorophenyl)-4-phenylbutanamide: A HDAC6 Inhibitor with Anti-proliferative Activity on Cervix Cancer and Leukemia Cells
Anti-Cancer Agents in Medicinal Chemistry Non-Human Primate Models for AIDS Vaccine Research
Current Drug Targets - Infectious Disorders