Zdzisław Szulc

(N,N-diethylamino)alkoxy derivatives of phenanthrolines asDNA binding agents

The interaction of the tricyclic angular azaaromatic system having positive charged side chains withDNA, influence of molecular structure of the ligand on the mode of noncovalent binding, and stability of the complex formed were established. Several (N,N-diethylamino)alkoxy derivatives of 1,7-, 1,8-, 1,10- and 4,7-phenanthroline in the protonated form were used as ligand. The electronic and steric factors were shown as responsible for the electrostatic and intercalative interactions of the ligand withDNA. The syntheses of (N,N-diethylamino)alkoxy derivatives from parent phenanthrolines were elaborated.ZusammenfassungDie Wechselwirkung von trizyklischen, azaaromatischen Systemen mit positiver Ladung an Seitenketten mitDNA, der Einfluß der molekularen Struktur des Liganden bei nonkovalenter Bindung und die Stabilität des gebildeten Komplexes wurde bestimmt. Als Liganden wurden mehrere (N,N-diethylamino)alkoxy-Verbindungen von 1,7-, 1,8-, 1,10- und 4,7-Phenanthrolin in protonierter Form benutzt. Es wurde gezeigt, daß die elektronischen und sterischen Faktoren für elektrostatische und intercalative Wechselwirkungen des Ligand undDNA verantwortlich sind. Es wurden Synthesen von (N,N-diethylamino)alkoxy-phenanthrolinen aus entsprechenden Chlorverbindungen ausgearbeitet.

N,N-diethylaminoalkoxy-4,7-phenanthrolines and 1,8-diazafluorene derivatives, a novel class of potential interferon inducers and antiviral agents: Interactions with nucleic acids in vitro and cellular activities

Tilorone aza-analogues, derivatives of 4,7-phenanthroline and 1,8-diazafluorene, were examined as DNA-complexing agents by spectral and electrophoretic methods. The binding process includes at least two types of interactions: electrostatic and, possibly, intercalation. Complex formation with the denatured DNA was also observed, but its nature remained unsolved. Binding and thermodynamic parameters were determined. All ligands studied showed weak antiviral activity and essentially no interferon induction when assayed in vitro and in vivo. It was concluded that interferon induction by tilorone may involve specific cell receptors or intermediaries.

Choline and halogen derivatives of CMA (9-oxo-10-acridine acetic acids) as tools for monitoring the interaction of the interferon inducers via a specific receptor

New choline and halogen derivatives of CMA (9-oxo-10-acridine acetic acid) were investigated as interferon (IFN) inducers in mice and in the mouse bone marrow-derived macrophage cultures. Two of the choline derivatives, DMCMA and CSCMA, were active IFN inducers presumably because they were hydrolyzed so as to release CMA. The halogen analogues of CMA were inactive or weak IFN inducers in vivo and in vitro. On the contrary, the Br and I derivatives of CMA were potent inhibitors of IFN induction by CMA in vitro. The behavior of the agonists and antagonists of CMA suggests that the induction of interferon may occur indirectly via a specific CMA-receptor complex.

The Synthesis of New Triazapolyphenes

The syntheses of three triaza-analogues of four-ring aromatic hydrocarbons: chino-[5,6-c]cinnoline 5, 4,5,10-triazychrysene 10 and 1,5,12-triazabenzo[c]phenanthrene 12 are presented and their UV spectra discussed. These compounds were obtained from the appropriate amines by the SKRAUP method. Synthese neuer Triazapolycyclen Es werden die Synthesen dreier Triazaanaloga von kondensierten Aromaten mit vier Benzolringen, Chino[5,6-c]cinnolin 5, 4,5,10-Triazachrysen 10 und 1,5,12-Triaza-benzo[c]-phenanthren 12, beschrieben und ihre UV-Spektren diskutiert. Die Verbindungen wurden aus den entsprechenden Aminen nach SKRAUP dargestellt.