The Study of Doxorubicin and its Interaction with Adenine by UV-Resonance Raman Spectroscopy

Lee, Chul Jae; Jung, Maeng Joon

doi:10.5012/jkcs.2008.52.2.118

Cited by 2 publications

(1 citation statement)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We selected the Topo IIα structure co‐crystallized with a DNA sequence (PDB: 4FM9) (Wendorff et al., 2012) since the reference drug doxorubicin was considered simultaneously as a DNA intercalator and a topoisomerase inhibitor (Lee et al., 2004). The protocol was validated by root‐mean‐square deviation (RMSD) with the co‐crystallized ligand of 0.35 Å. Additionally, the pH was considered according to the bibliography of the intracellular environment, pH of 7.2 (Swietach et al., 2007).…”

Section: Resultsmentioning

confidence: 99%

Evaluation of doxorubicin and β‐lapachone analogs as anticancer agents, a biological and computational study

Mercado‐Sánchez,

López,

Chávez‐Rocha

et al. 2024

Chem Biol Drug Des

View full text Add to dashboard Cite

We have conducted an experimental and computational evaluation of new doxorubicin (4a–c) and β‐lapachone (5a–c) analogs. These novel anticancer analogs were previously synthesized, but had not been tested or characterized until now. We have evaluated their antiproliferative and DNA cleavage inhibition properties using breast (MCF‐7 and MDA‐MB‐231) and prostate (PC3) cancer cell lines. Additionally, cell cycle analysis was performed using flow cytometry. Computational studies, including molecular docking, pharmacokinetic properties, and an analysis of DFT and QTAIM chemical descriptors, were performed to gain insights into the electronic structure and elucidate the molecular binding of the new β‐lapachone and doxorubicin analogs with a DNA sequence and Topoisomerase II (Topo II)α. Our results show that 4a analog displays the highest antiproliferative activity in cancer cell lines by inducing cell death. We observed that stacking interactions and hydrogen bonding are essential to stabilize the molecule‐DNA‐Topo IIα complex. Moreover, 4a and 5a analogs inhibited Topo's DNA cleavage activity. Pharmacodynamic results indicated that studied molecules have favorable adsorption and permeability properties. The calculated chemical descriptors indicate that electron accumulation in quinone rings is relevant to the reactivity and biological activity. Based on our results, 4a is a strong candidate for becoming an anticancer drug.

show abstract

Section: Resultsmentioning

confidence: 99%