Medicinal Chemistry - Online First
Description text for Online First listing goes here...
21 - 24 of 24 results
-
-
Imidazole-Based Metal Complex Derivatives: A Comprehensive Overview of Synthesis and Biological Applications
Available online: 30 October 2024More LessThe imidazole scaffold is a cornerstone in medicinal chemistry, widely recognized for its extensive range of biological activities and ability to form stable metal complexes. This review article provides a detailed overview of recent advancements in synthesizing, characterization, and biological evaluation of metal-complexed imidazole derivatives. We explored various synthetic strategies to create diverse metal-based imidazole complexes, emphasizing innovations that enhance efficiency and yield. Furthermore, we delve into the biological profiling of imidazole derivatives, summarizing key findings from studies investigating their antimicrobial, antifungal, anticancer, and other therapeutic properties. Special attention is given to metal coordination's role in modulating these compounds' biological activity. The review discusses the synthesis of imidazole-metal complexes, illustrating how metal ions such as copper, zinc, and iron enhance the pharmacological profiles of imidazole derivatives. Thus, the data from numerous studies was collated and analyzed to comprehensively understand the current landscape and future prospects in imidazole chemistry associated with metals. It is a valuable resource for researchers, guiding future investigations and fostering the development of novel metal-based imidazole therapeutics.
-
-
-
A Review of the Medicinal Importance and Perspectives of the 2-isoxazoline Scaffold
Authors: Shilpi Pathak, Pooja Singh and Gaurav JadonAvailable online: 28 October 2024More LessThe 2-isoxazoline scaffold has emerged as a key structure in medicinal chemistry, with great therapeutic potential for a wide range of biological targets. This review investigates the medicinal value of the 2-isoxazoline scaffold, emphasizing its adaptability and usefulness in the development of new medications. Isoxazoline has a wide range of biological actions, including antibacterial, anti-inflammatory, anticancer, and anti-parasitic effects, which are due to their distinct structural features and capacity to interact with a variety of biological processes. The synthesis, functionalization, and pharmacological uses of isoxazoline derivatives are rigorously studied, yielding information about their modes of action and therapeutic value. This review emphasizes the promise of isoxazoline-based molecules in tackling current medical difficulties and lays the way for future research in this vibrant field of medicinal chemistry.
-
-
-
Heterocyclic Compounds as Bcr-Abl Tyrosine Kinase Inhibitors Against Chronic Myeloid Leukemia
Authors: Sarah Gado, Mohammed Al-Kassim Hassan, Mehmet Murat Kisla and Zeynep Ates-AlagozAvailable online: 11 October 2024More LessDespite significant progress in oncology therapeutics, cancer remains a leading cause of mortality worldwide. Chronic myeloid leukemia, which accounts for 15% of all adult leukemia cases, is characterized by chromosomal abnormalities involving the fusion of the Bcr and Abl genes to form the Bcr-Abl oncogene. Current drug treatment of the disease involves the use of Bcr-Abl tyrosine kinase inhibitors belonging to the first, second, and third generations. However, the toxicity and resistance associated with the use of imatinib, a first-generation Bcr-Abl inhibitor, in cases where the T315I mutation exists, necessitates the need for new tyrosine kinase inhibitors. This review focuses on recent synthetic compounds that exhibit potential as inhibitors of the Bcr-Abl protein which could be utilized in chemotherapy. Herein, we evaluated and summarized 36 studies published in the last few years that reported on newly synthesized and biologically evaluated novel small molecules with different heterocyclic scaffolds as Bcr-Abl tyrosine kinase inhibitors. The intricacy of the structure of newly synthesized compounds and the fact that each compound contains more than one scaffold makes it difficult to infer the potentially active core or scaffold. However, investigating different combined scaffolds enhances the chance of successfully developing novel drug candidates. Overall, the information provided in this review can be beneficial to researchers with an interest in chronic myeloid leukemia and tyrosine kinase inhibitors.
-
-
-
Design and Development of [1,2,4]Triazolo[4,3-b][1,2,4]triazines as Potential Anticancer Agents with Genotoxicity and Apoptotic Activity
Available online: 09 October 2024More LessAims: In this current study, a new series of triazolo-triazine derivatives were designed and synthesized as potential anticancer agents. Methods: The antiproliferative activity of the new compounds was evaluated against three different cancerous cell lines (MDA-MB-231, HCT-116, A549, and HT-29) using an MTT assay. To evaluate the mechanism of action, the ability of the best compound in apoptosis induction and DNA damage was evaluated using the flow cytometry technique and comet assays. Furthermore, molecular docking simulation was used to investigate their interactions with the two targets, VEGFR2 and c-Met kinases. Results: Results showed that 6-(4-bromophenyl)-3-((4-methoxybenzyl)thio)-[1,2,4]triazolo[4,3-b][1,2,4]triazine (8c) demonstrated the best anti-proliferative activity against the human colorectal carcinoma cells HCT-116 with an IC50 value of 38.7 ± 1.7 µM. In silico evaluations showed that the triazolo-triazine scaffold, along with the methoxy substitution of compound 8c, was involved in creating effective H-bond interactions in the active site of both targets. Conclusion: Our results showed that compound 8c significantly increased cell death through apoptosis induction and caused a significant increase in genotoxicity. Furthermore, it was found that the tested compound 8c, with a selectivity index of 1.74, possessed selective antiproliferative activity towards the colorectal cancer cell line HCT-116 compared to the normal fibroblast cell line. These findings could be useful in the development of novel VEGFR2/c-Met dual-targeted inhibitors in the future.
-