Abstract
A new series of phenothiazine and carbazole derivatives was synthesized and evaluated for their biological activity on human protein farnesyltransferase. The farnesyltransferase assays revealed that carbazole 4f was the best farnesyltransferase inhibitor in the current study (IC50 (human FTase) = 35.0 µM), providing that the presence of the carbazole unit is important in this family of compounds. Moreover, unexpected disulfide analogues were observed during coupling reactions of activated esters 12 and 13 with aminoethanethiol and mercaptoethanol, respectively. These dimers deserve further chemical and biological investigation in order to develop new chemical entities for anticancer research.
Keywords: Anticancer agent, carbazole, disulfide, farnesyltransferase, phenothiazine.
Letters in Drug Design & Discovery
Title:Investigation of New Phenothiazine and Carbazole Derivatives as Potential Inhibitors of Human Farnesyltransferase
Volume: 12 Issue: 2
Author(s): Gina-Mirabela Dumitriu, Alina Ghinet, Dalila Belei, Benoit Rigo, Philippe Gautret, Joelle Dubois and Elena Bicu
Affiliation:
Keywords: Anticancer agent, carbazole, disulfide, farnesyltransferase, phenothiazine.
Abstract: A new series of phenothiazine and carbazole derivatives was synthesized and evaluated for their biological activity on human protein farnesyltransferase. The farnesyltransferase assays revealed that carbazole 4f was the best farnesyltransferase inhibitor in the current study (IC50 (human FTase) = 35.0 µM), providing that the presence of the carbazole unit is important in this family of compounds. Moreover, unexpected disulfide analogues were observed during coupling reactions of activated esters 12 and 13 with aminoethanethiol and mercaptoethanol, respectively. These dimers deserve further chemical and biological investigation in order to develop new chemical entities for anticancer research.
Export Options
About this article
Cite this article as:
Dumitriu Gina-Mirabela, Ghinet Alina, Belei Dalila, Rigo Benoit, Gautret Philippe, Dubois Joelle and Bicu Elena, Investigation of New Phenothiazine and Carbazole Derivatives as Potential Inhibitors of Human Farnesyltransferase, Letters in Drug Design & Discovery 2015; 12 (2) . https://dx.doi.org/10.2174/1570180811666140909010435
DOI https://dx.doi.org/10.2174/1570180811666140909010435 |
Print ISSN 1570-1808 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-628X |
- 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
-
Aptamers in Drug Design: An Emerging Weapon to Fight a Losing Battle
Current Drug Targets Synthetic and Biological Vesicular Nano-Carriers Designed for Gene Delivery
Current Pharmaceutical Design Molecular Classification and Drug Response Prediction in Cancer
Current Drug Targets Antiangiogenesis and Radiotherapy: What Is the Role of Combined Modality Treatment?
Current Medicinal Chemistry - Anti-Cancer Agents Editorial: [Hot Topic: Antidotes and Rescue Therapies]
Current Pharmaceutical Biotechnology Intestinal Absorption and Presystemic Elimination of Various Chemical Constituents Present in GBE50 Extract, a Standardized Extract of Ginkgo biloba Leaves
Current Drug Metabolism CD147/EMMPRIN and CD44 are Potential Therapeutic Targets for Metastatic Prostate Cancer
Current Cancer Drug Targets Antineoplastic Chemotherapy Induced QTc Prolongation
Current Drug Safety Quantum Dots in the Therapy: Current Trends and Perspectives
Mini-Reviews in Medicinal Chemistry Reflections on MicroRNAs in Chronic Pulmonary Disease: Looking into the miR-ror and Crystal Ball
Inflammation & Allergy - Drug Targets (Discontinued) PDGF/PDGFR Signaling and Targeting in Cancer Growth and Progression: Focus on Tumor Microenvironment and Cancer-associated Fibroblasts
Current Pharmaceutical Design Discovery of Selective Probes and Antagonists for G Protein-Coupled Receptors FPR/FPRL1 and GPR30
Current Topics in Medicinal Chemistry Transcriptome Analysis of FEN1 Knockdown HEK293T Cell Strain Reveals Alteration in Nucleic Acid Metabolism, Virus Infection, Cell Morphogenesis and Cancer Development
Combinatorial Chemistry & High Throughput Screening Recent Advances in Diagnostic and Therapeutic Approaches for Breast Cancer: A Comprehensive Review
Current Pharmaceutical Design Tumour Reactions to Hypoxia
Current Molecular Medicine Drug Targeting Strategies for Photodynamic Therapy
Anti-Cancer Agents in Medicinal Chemistry Resveratrol and Cancer: Chemoprevention, Apoptosis, and Chemoimmunosensitizing Activities
Current Medicinal Chemistry - Anti-Cancer Agents Inflammation in Ischemic Stroke: Mechanisms, Consequences and Possible Drug Targets
CNS & Neurological Disorders - Drug Targets Mechanisms of Drug Resistance to Vascular Endothelial Growth Factor (VEGF) Inhibitors
Anti-Cancer Agents in Medicinal Chemistry Cell Responses to Oxidative Stressors
Current Pharmaceutical Design