Effect of distamycin A and congocidine on DNA synthesis by rous sarcoma virus reverse transcriptase

Structure-activity relationships of pyrrole amidine antiviral antibiotics. 2. Preparation of mono- and tripyrrole derivatives of congocidine

“…This phenomenon indicates the possibility of a separation between the cytotoxicity and the antiviral activity. In all the tests we checked, the tripyrrole derivatives of congocidines (7-9) were more potent and less cytotoxic than congocidine and its monopyrrole homologue (16). A nice correlation between the increased number of pyrrole rings (n) in the molecule (from one to three) and the increased antiviral activity was demonstrated in the congocidine series.…”

“…d-[IV-Methyl-4-(guanidineacetamido)pyrrole-2-carboxamidojpropionamidine Dihydrochloride (16). This compound Book Reviews was prepared from the nitropyrrole 14 as described above for the synthesis of its homologue 7.…”

“…11 Congocidine has very interesting biological activities, such as antibacterial,12 antiparasitic,2,3,10 and antiviral. As an antiviral drug, congocidine inhibits the multiplication of DNA viruses, such as vaccinia virus,5,13 HSV,14 and SFV,15 5and reteroviruses, such as RSV, 16 RuLV,17 and FeLV. 18 Congocidine and distamycin A19 (2) are the major OHCHN (1) Corresponding address: Pharmacy Department, School of Pharmacy, Hebrew University, Jerusalem, Israel.…”

“…(c) The monopeptide homologue of congocidine (16) was prepared from the known nitro amidine (14)24 in a way similar to that described previously (Scheme II). The nitro amidine (14)24 was catalytically reduced to the amino amidine (15), which was reacted with glycocyamine hydrochloride (13) in the presence of DCC (Scheme II), giving the desired congocidine.…”

Biological activity and DNA Sequence Specificity of Synthetic Carbamoyl Analogues of Distamycin

“…The footprinting data are fully consistent with previous studies showing that the terminal forrnamido group can be replaced with other entities such as a thioformyl group (Zimmermann et al, 1991;Singh et al, 1992) without markedly affecting the capacity of the ligand to recognize preferentially AT-rich sequences in DNA. Early studies on distamycin analogues showed that an increase in the number of N-methylpyrrolecarboxamide residues generally correlates with an increase in the affinity of the drug for DNA as well as its antiviral activity (Zimmer et al, 1972;Chandra et al, 1972;Kotler & Becker, 1972). But the gain in activity was relatively low: for example, the selectivity index (IC so ce11lIC so virus) was found to be only three times higher with the formyl amino derivative 3, with five N-methylpyrrolecarboxamide residues, than with distamycin (Chandra et al, 1972).…”