Interaction of Acridine Drugs With Dna and Nucleotides

Abstract

Abstract-At high phosphate-to-drug ratios acridine drugs intercalate between hydrogen bonded DNA base pairs causing significant changes in the physico-chemical properties of DNA. The determination of the nature of the strong (or primary) interaction between acridine drugs and DNA is of great importance for elucidating the mode of the biological action of the drugs.Nanosecond measurements have revealed a fast depolarization of the fluorescence of proflavine, one of the most extensively studied acridines, bound to DNA. The electronic structure of the complex, however, is not substantially altered during the lifetime of the excited singlet electronic state of the drug. Guanine has been shown to be responsible for the quenching of the proflavine fluorescence upon binding to DNA. A temperature-jump relaxation study has demonstrated a rather external complexation of this drug with the G-C base pairs; this complex, whose formation occurs in the strong binding region, is distinct from the weak electrostatic complex.The findings that the binding ability of a series of acridines correlates with their basicity and that the drug-binding behavior of methylated DNA is significantly different from that of DNA suggested that specific forces may be also involved in the drug-DNA binding in addition to hydrophobic forces. Recent experiments employing molecular complexes of acridines with nucleotides as model systems have provided strong support for the specificity of the drug-DNA interaction. Hydrogen bonding between the drug and reactive groups of the DNA bases that do not contribute directly to the stability of the helix may be involved in that interaction.The stoichiometry of the proflavine-guanosine 5'-phosphate complex is 1 : 1. Its association constant increases from 310 M -' , when proflavine is in its ground electronic state, to 1550 M -' , when proflavine is in its first excited singlet state. Thus, light absorbed by the drug alters its reactivity which, in turn, results in an appreciable increase in its ability to bind to the nucleotide. In view of the proposed importance of the drug-base interaction in explaining the mutagenic properties of acridine drugs and, in particular, of the proposed involvement of the G-C base pairs, this finding emphasizes the possible importance of drug photoexcitation in acridine mutagenesis; it also contributes to the elucidation of photodynamic action.X-ray diffraction studies have recently provided very interesting demonstrations of strong binding of 9-aminoacridine and of the phenanthridine drug ethidium bromide to adenine-uracil base pairs in the crystalline phase.The ability of photoexcited acridine drugs to inactivate viruses has been recently used for therapeutic purposes. The carcinogenic risk involved, however, is still under investigation.

Interactions of quercetin and its lanthane complex with double stranded DNA/RNA and single stranded RNA: Spectrophotometric sensing of poly G

“…In addition, equally pronounced spectroscopic selectivity was observed in UV/vis titrations upon binding Q to poly G. However, selective spectroscopic answer of Q upon binding to poly G was not reflected on the affinity, since Q forms with all studied ss-polynucleotides noncovalent complexes of similar stability (Ks). The mechanistic explanation of specific spectroscopic effects of poly G addition to Q could be correlated with electron donating properties of guanine [36,37] and possibly with selective oxidation of guanines by quercetin-metal complexes [38]. Similar effects were elaborated on proflavine [36] and 4,9-diazapyrene [39] derivative (increase of fluorescence for all bases, quenching for guanine derivatives).…”

“…The mechanistic explanation of specific spectroscopic effects of poly G addition to Q could be correlated with electron donating properties of guanine [36,37] and possibly with selective oxidation of guanines by quercetin-metal complexes [38]. Similar effects were elaborated on proflavine [36] and 4,9-diazapyrene [39] derivative (increase of fluorescence for all bases, quenching for guanine derivatives). It is important to stress that changes of Q UV/vis spectrum induced by addition of poly G are significantly stronger than ones induced by poly G-poly C. This finding points toward essential role of the free poly G sequence (not hydrogen bonded in double helix) in spectroscopic recognition by Q.…”

Cell attachment to extracellular matrices is modulated by pulsed radiation at 820 nm and chemicals that modify the activity of enzymes in the plasma membrane

“…The antimalarial drug quinacrine (mepacrine, atebrin) is often used as a non-selective inhibitor of all the isoforms of the PLA 2 [24,25]. At the same time, quinacrine like other acridins intercalates nucleic acids [26], reduces the membrane potential in mitochondria and causes their ultrastructural changes [27], inhibits the electrogenic K transport [18] as well as the Na /Ca 2 exchange [28] through the plasma membrane. Quinacrine is also known to inhibit¯avoproteins and calmodulin [29,30].…”

Binding of fluorescent acridine dyes acridine orange and 9-aminoacridine to hemoglobin: Elucidation of their molecular recognition by spectroscopy, calorimetry and molecular modeling techniques

“…The better antitumoral activity of 9AA over AO has been ascribed to various activities such as p53 activation and inhibition of NF-κB and Bcl-xL proteins [16]. It has long been known to be a potent frame shift mutagen in viruses and bacteria [17][18][19][20][21]. 9AA inhibits HIV-1 of Tat dependent transcription which activates p53 without inducing apoptosis [22].…”