Structure-activity relationships of pyrroleamidine antiviral antibiotics. 1. Modifications of the alkylamidine side chain

Abstract

Representatives of three types of side-chain analogues of distamycin A (1) were synthesized. These were tested for cytotoxicity, inhibition of herpes simplex virus (HSV) replication in cultured cells, effects on the synthesis of HSV DNA in isolated nuclei in vitro, as well as on DNA synthesis by purified HSV DNA polymerase. Distamycin A was the most active compound in all three antiviral tests, as well as the most toxic. However, several compounds, in particular the aromatic analogues 15 and 16, showed no toxicity under the experimental conditions used but were still very active in the three antiviral tests.

DNA polymerase in nuclei isolated from herpes simplex virus type-2-infected cells. Characterization of the reaction product and inhibition by substrate analogs

“…Beside providing the replication complex not present in isolated en-zymes, nuclei are permeable to substrates and inhibitors thereby permitting quantitative studies not possible in whole cells. This approach has been used with nuclei from HSV-l-infected cells [6,8,9,14,15] but to our knowledge nuclei from HSV-2-infected cells have not been utilized for the study of inhibitors of herpesvirus replication.…”

Structure–activity relationships of pyrrole amidine antiviral antibiotics III: Preparation of distamycin and congocidine derivatives based on 2,5-disubstituted pyrroles

“…The tripyrrole compounds tested showed less antiviral activity than distamycin A and the tripyrrole derivatives of congocidine (17,20). Apparently, the peptide bond a t positions 2 and 4 of the pyrrole rings is critical for the antiviral activity in the distamycin or congocidine series.…”

“…The details of these techniques were given previously (17). The details of these techniques were given previously (17).…”

Antioxidant Activity of some Amidine Derivatives

“…Several methods to quantify the antioxidant activity of natural or synthetic compounds are at hand [4,5]. Of the synthetic compounds, amidines and their derivatives stand as valuable substances in various biological and industrial fields, namely medicine [6][7][8]. In fact, they have been reported to have multiple biological effects, including anticancer, antitumor, antiviral, antifungal and antimicrobial activities [8,9].…”

“…Of the synthetic compounds, amidines and their derivatives stand as valuable substances in various biological and industrial fields, namely medicine [6][7][8]. In fact, they have been reported to have multiple biological effects, including anticancer, antitumor, antiviral, antifungal and antimicrobial activities [8,9]. They are also important intermediates in the field of organic synthesis [10], especially for the preparation of various heterocyclic compounds [11].…”