Antiprotozoal activity and DNA binding of N-substituted N-phenylbenzamide and 1,3-diphenylurea bisguanidines

Abstract

The compounds were tested against T. b. rhodesiense and P. falciparum.N-alkylated compounds 7b and 7c were 100% curative in the STIB900 mouse model of HAT.DNA binding affinity was measured by SPR with AATT, (AT) 4 and (CG) 4 hairpin duplexes.7b and 7c bind selectively to AT-rich DNA.

Bisimidazoline arylamides binding to the DNA minor groove: N1-hydroxylation enhances binding affinity and selectivity to AATT sites

“…3,4,7 In previous studies, we have discovered diphenyl dicationic compounds 1-5 (Chart 1) that showed excellent in vivo activity against African trypanosomes (T. b. rhodesiense) in mouse models of sleeping sickness. [9][10][11][12] The binding interaction of 5 with the minor groove of the all-AT DNA sequence dIJAAAATTTT) 2 and with the selfcomplimentary nucleotide dIJCTTAATTCGAATTAAG) 2 was demonstrated by X-ray crystallography. 13,14 Nagle et al showed that arylamide derivatives 1 and 2 bound strongly and selectively to AT oligonucleotides with a slight preference (2-to 3-fold) for dsDNA CGAATTCG vs. CATATATAT sequences.…”

A New Nonpolar N -Hydroxy Imidazoline Lead Compound with Improved Activity in a Murine Model of Late-Stage Trypanosoma brucei brucei Infection Is Not Cross-Resistant with Diamidines

“…Regarding the mode of action of the antitrypanosomal lead compounds I to V, earlier studies have shown that this class of dicationic compounds binds to the DNA minor groove at AT-rich sequences (55)(56)(57)(58). In trypanosomes, the kinetoplast DNA (kDNA) has a high content of AT-rich regions that could be a site of selective action of this kind of compound (59).…”

Crystal structure of 4-bromo-N-(2-hydroxyphenyl)benzamide

“…For the antiprotozoal and antimicrobial properties of phenylbenzamides, see: Ríos Martínez et al (2014); Ş ener et al (2000). For active metabolites of benzoxazoles, see: Mobinikhaledi et al (2006).…”

“…The crystal structure determination of the title compound (I), is part of a study on phenylbenzamides carried out in our research group, and they are synthesized from the reaction of picryl benzoates with 2-hydroxy-aniline. These compounds have received extensive attention because of their antiprotozoal (Ríos Martínez et al, 2014) and anti-microbialactivity (Şener et al, 2000), and as active metabolites of benzoxazoles (Mobinikhaledi et al, 2006). They have also been studied as inhibitors of tyrosine kinases (Capdeville et al, 2002) and inducers of apoptosis in the tumor development process (Olsson et al, 2002).…”