13138-78-8Relevant articles and documents
Novel distamycin analogues that block the cell cycle of African trypanosomes with high selectivity and potency
Comini, Marcelo A.,Franco, Jaime,Scarone, Laura
, (2020/01/25)
Polyamides-based compounds related to the Streptomycetal distamycin and netropsin are potent cytostatic molecules that bind to AT-rich regions of the minor groove of the DNA, hence interfering with DNA replication and transcription. Recently, derivatives belonging to this scaffold have been reported to halt the proliferation of deadly African trypanosomes by different and unrelated mechanisms. Here we describe the synthesis and preliminary characterization of the anti-trypanosomal mode of action of new potent and selective distamycin analogues. Two tri-heterocyclic derivatives containing a central N-methyl pyrrole ring (16 and 17) displayed high activity (EC50 5000 with respect to mammalian macrophages) against the infective form of T. brucei. Both compounds caused cell cycle arrest by blocking the replication of the mitochondrial DNA but without affecting its integrity. This mode of action clearly differs from that reported for classical minor groove binder (MGB) drugs, which induce the degradation of the mitochondrial DNA. In line with this, in vitro assays suggest that 16 and 17 have a comparatively lower affinity for different template DNAs than the MGB drug diminazene. Therapeutic efficacy studies and stability assays suggest that the pharmacological properties of the hits should be optimized. The compounds can be rated as excellent scaffolds for the design of highly potent and selective anti-T. brucei agents.
Ortho -Fluoroazobenzene derivatives as DNA intercalators for photocontrol of DNA and nucleosome binding by visible light
Heinrich, Benedikt,Bouazoune, Karim,Wojcik, Matthias,Bakowsky, Udo,Vázquez, Olalla
, p. 1827 - 1833 (2019/02/20)
We report a high-affinity photoswitchable DNA binder, which displays different nucleosome-binding capacities upon visible-light irradiation. Both photochemical and DNA-recognition properties were examined by UV-Vis, HPLC, CD spectroscopy, NMR, FID assays,
ELIMINATION OF HEPATITIS B VIRUS WITH ANTIVIRAL AGENTS
-
Page/Page column 97; 89, (2017/09/27)
The present invention is directed to compounds, compositions and methods for preventing, treating or curing Hepatitis B (HBV) infection in human subjects or other animal hosts. The compounds are as also pharmaceutically acceptable, salts, prodrugs, and other derivatives thereof as pharmaceutical compositions and methods for treatment, prevention or eradication of HBV infection.
