Elucidation of binding interactions and mechanism of Fludarabine with dsDNA via multispectroscopic and molecular docking studies

Publication date: Available online 17 November 2019Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Pelin Şenel, Soykan Agar, V. Oyku Sayin, Filiz Altay, Mine Yurtsever, Ayşegül GölcüAbstractFludarabine is a purine derivative, anti-neoplastic drug and is still being used in the treatments of chronic lymphocytic leukemia, small lymphocytic lymphoma, acute myeloid leukemia, Non-Hodgkin’s lymphoma. It achieves its function by interacting with DNA. Therefore, the binding interactions of such drugs with deoxyribonucleic acid (DNA) is an important subject for pharmaceutical and biochemical studies aiming at designing better DNA binding drugs. Although DNA binding mode of some of the anti-neoplastic drugs has been studied, DNA interaction of Fludarabine has not been explored yet. For this reason, this work has been dedicated to deciphering the experimental and theoretical investigation of Fludarabine binding mechanism via multispectroscopic techniques including UV absorption spectroscopy, thermal denaturation, fluorescence and FTIR spectroscopy, electrochemical and viscosity measurement methods as well as with molecular docking studies under physiological conditions. We observed in the lowest energy docking poses that Fludarabine binds to DNA via major groove binding mode. The nonplanar and extended structure and hydrogen bonding interactions of Fludarabine with the Adenine-Thymine base-pair played a very decisive role in the binding mode as...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research

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ConclusionVenetoclax therapy in a real-world cohort offered modest benefits in heavily pretreated patients. Adverse events were observed at a greater incidence than in the clinical trials. A wide heterogeneity of venetoclax dose escalation, multiagent combinations, and timing of initiation were identified and require investigation in subsequent clinical trials.
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
ConclusionWe suggest a one ‐compartment population model with first‐order elimination to capture the pharmacokinetic profile for basiliximab for this patient population.
Source: Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy - Category: Drugs & Pharmacology Authors: Tags: ORIGINAL RESEARCH ARTICLE Source Type: research
ConclusionVenetoclax therapy in a real-world cohort offered modest benefits in heavily-pretreated patients. Adverse events were observed at higher incidence compared to clinical trials. A wide heterogeneity of venetoclax dose escalation, multi-agent combinations, and timing of initiation were identified and would best be investigated in subsequent clinical trials.
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
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Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Leukemias, Lymphoma, Hematologic Malignancies, Health Outcomes and Economics of Cancer Care Source Type: research
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Source: Experimental Hematology - Category: Hematology Authors: Tags: Brief Communication Source Type: research
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Source: Drugs - Category: Drugs & Pharmacology Source Type: research
(H. Lee Moffitt Cancer Center&Research Institute) Researchers from Moffitt Cancer Center and Dana-Farber Cancer Institute have discovered a mechanism of drug resistance to Venetoclax ® , also known as ABT-199, a BCL-2 targeting drug commonly used to treat chronic lymphocytic leukemia and acute myeloid leukemia. Their findings, published in the journal Cancer Cell, also suggest a possible co-treatment strategy to overcome this resistance.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
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Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
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Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
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