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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CONCLUSIONS: There was no convincing evidence of an increased risk in any hematological malignancy when interpreting the results from both series of analyses. PMID: 32818321 [PubMed - as supplied by publisher]
Source: Transfusion - Category: Hematology Authors: Tags: Transfusion Source Type: research
Acute myeloid leukemia (AML) in the setting of Noonan syndrome (NS) has been reported before without clear guidelines for treatment or prognosis in these subgroups of patients, most likely due to its rarity and incomplete understanding of the pathogenesis of both diseases. In the current era of next-generation sequencing-based genomic analysis, we can better identify patients with NS with more accurate AML-related prognostic markers. Germline mutations inPTPN11 are the most common cause of NS. Somatic mutations inNPM1 occur frequently in AML. Here, we describe a young adult patient with a novel combined germlinePTPN11 and ...
Source: Acta Haematologica - Category: Hematology Source Type: research
Abstract Acute myeloid leukemia (AML) in the setting of Noonan syndrome (NS) has been reported before without clear guidelines for treatment or prognosis in these subgroups of patients, most likely due to its rarity and incomplete understanding of the pathogenesis of both diseases. In the current era of next-generation sequencing-based genomic analysis, we can better identify patients with NS with more accurate AML-related prognostic markers. Germline mutations in PTPN11 are the most common cause of NS. Somatic mutations in NPM1 occur frequently in AML. Here, we describe a young adult patient with a novel combined...
Source: Acta Haematologica - Category: Hematology Authors: Tags: Acta Haematol Source Type: research
Basel, 23 March 2020 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the phase III VIALE-A study met its dual primary endpoints of overall survival and composite complete remission rate (CR + CRi). Venclexta ®/Venclyxto® (venetoclax) in combination with azacitidine, a hypomethylating agent, showed a statistically significant improvement in overall survival in people with previously untreated acute myeloid leukaemia (AML) who were ineligible for intensive induction chemotherapy, compared to azacitidine alone. Safety for Venclexta/Venclyxto plus azacitidine appeared consistent with the known safety profile ...
Source: Roche Media News - Category: Pharmaceuticals Source Type: news
hazib Pervaiz Deregulated cellular apoptosis is a hallmark of cancer and chemotherapy resistance. The B-cell lymphoma 2 (BCL-2) protein family members are sentinel molecules that regulate the mitochondrial apoptosis machinery and arbitrate cell fate through a delicate balance between pro- and anti-apoptotic factors. The recognition of the anti-apoptotic BCL2 gene as an oncogenic driver in hematological malignancies has directed attention toward unraveling the biological significance of each of the BCL-2 superfamily members in cancer progression and garnered interest in the targeting of apoptosis in cancer therapy. Acco...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Basel, 31 January 2020 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the European Medicines Agency ’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for Venclyxto® (venetoclax) in combination with Gazyvaro® (obinutuzumab) for the treatment of adults with previously untreated chronic lymphocytic leukaemia (CLL).“Despite advances in treating chronic lymphocytic leukaemia, many patients cannot tolerate the side effects of chemotherapy-containing regimens,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product ...
Source: Roche Investor Update - Category: Pharmaceuticals Source Type: news
AbstractPurpose of ReviewThis review highlights the importance of the Bcl-2 family members in lymphoma cell survival and discusses the approaches to modulate their function, directly or indirectly, to advance lymphoma therapeutics.Recent FindingsThe balance of cell death versus survival is ultimately leveraged at the mitochondria. Mitochondrial outer membrane permeabilization (MOMP) is the critical event that governs the release of pro-apoptotic molecules from the intermembrane mitochondrial space. MOMP is achieved through the coordinated actions of pro- and anti-apoptotic Bcl-2 family member proteins. Recognition of funct...
Source: Current Oncology Reports - Category: Cancer & Oncology Source Type: research
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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