Investigation of Decitabine Effects on HDAC3 and HDAC7 mRNA Expression in NALM-6 and HL-60 Cancer Cell Lines

Dalvand, Sina; Namdari, Amin; Sepahvand, Farzad; Meshkibaf, Mohammad Hassan; Ahmadpour, GholamReza

doi:10.52547/rbmb.10.3.420

Cited by 1 publication

(1 citation statement)

References 34 publications

(36 reference statements)

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“…Indeed, Gemcitabine has broad anti-leukemic activity across different AML subtypes and is more effective than Ara-C, both in vitro and in vivo [ 52 ]. Our results are also in a good agreement with the preclinical studies, which indicated that Decitabine is a more effective anti-leukemic agent than 5-azacytidine [ 53 ], but five times less effective than Ara-C [ 54 ]. The mechanism of action of 5-azacytidine is different and involves primarily DNA hypomethylation.…”

Section: Resultssupporting

confidence: 90%

Butterfly Effect in Cytarabine: Combined NMR-NQR Experiment, Solid-State Computational Modeling, Quantitative Structure-Property Relationships and Molecular Docking Study

Latosińska,

Seliger

et al. 2024

Pharmaceuticals

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Cytarabine (Ara-C) is a synthetic isomer of cytidine that differs from cytidine and deoxycytidine only in the sugar. The use of arabinose instead of deoxyribose hinders the formation of phosphodiester linkages between pentoses, preventing the DNA chain from elongation and interrupting the DNA synthesis. The minor structural alteration (the inversion of hydroxyl at the 2′ positions of the sugar) leads to change of the biological activity from anti-depressant and DNA/RNA block builder to powerful anti-cancer. Our study aimed to determine the molecular nature of this phenomenon. Three 1H-14N NMR-NQR experimental techniques, followed by solid-state computational modelling (Quantum Theory of Atoms in Molecules, Reduced Density Gradient and 3D Hirshfeld surfaces), Quantitative Structure–Property Relationships, Spackman’s Hirshfeld surfaces and Molecular Docking were used. Multifaceted analysis—combining experiments, computational modeling and molecular docking—provides deep insight into three-dimensional packing at the atomic and molecular levels, but is challenging. A spectrum with nine lines indicating the existence of three chemically inequivalent nitrogen sites in the Ara-C molecule was recorded, and the lines were assigned to them. The influence of the structural alteration on the NQR parameters was modeled in the solid (GGA/RPBE). For the comprehensive description of the nature of these interactions several factors were considered, including relative reactivity and the involvement of heavy atoms in various non-covalent interactions. The binding modes in the solid state and complex with dCK were investigated using the novel approaches: radial plots, heatmaps and root-mean-square deviation of the binding mode. We identified the intramolecular OH···O hydrogen bond as the key factor responsible for forcing the glycone conformation and strengthening NH···O bonds with Gln97, Asp133 and Ara128, and stacking with Phe137. The titular butterfly effect is associated with both the inversion and the presence of this intramolecular hydrogen bond. Our study elucidates the differences in the binding modes of Ara-C and cytidine, which should guide the design of more potent anti-cancer and anti-viral analogues.

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Section: Resultssupporting

confidence: 90%