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Design, Synthesis, DNA Binding, Cytotoxicity, and Molecular Docking Studies of Amonafide‐Linked β ‐Lactam
Author(s) -
Rad Javad Ameri,
Jarrahpour Aliasghar,
Aseman Marzieh Dadkhah,
Nabavizadeh Masoud,
Pournejati Roya,
KarbalaeiHeidari Hamid Reza,
Turos Edward
Publication year - 2019
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201803785
Subject(s) - ethidium bromide , acridine orange , chemistry , lactam , dna , gel electrophoresis , cytotoxicity , acridine , stereochemistry , intercalation (chemistry) , electrophoretic mobility shift assay , biochemistry , organic chemistry , in vitro , transcription factor , apoptosis , gene
This study describes our investigations on the synthesis, molecular modeling, and biological capabilities of a new β ‐lactam containing the anticancer agent, amonafide. This is the first time that amonafide has been applied to a β ‐lactam synthesis, which involved five steps from naphthalic anhydride. The β ‐lactam was structurally characterized by FT‐IR, 1 H NMR, 13 C NMR, mass spectra, and elemental analysis. UV‐vis and fluorescence spectroscopy studies indicated that the β ‐lactam is an effective DNA intercalating agent. Gel electrophoresis confirmed its intercalation into the pBluescript plasmid DNA, causing a considerable decrease in its electrophoretic mobility. The gel electrophoresis pattern in the presence of ethidium bromide, acridine orange, and methyl green also demonstrated that the β ‐lactam was stacked tightly between DNA bases via the major groove. Moreover, the MTT assay of the β ‐lactam against the HepG2 cancerous cell line showed potential cytotoxic behavior with an IC 50 of 65.5 μ M and 34.2 μ M after 48 and 72 h incubation, respectively. Molecular docking experiments were also in agreement with the experimental data and showed the major groove binding behavior of the β ‐lactam.