Exploiting a basic chemosensitizing pharmacophore hypothesis. Part 1: Synthesis and biological evaluation of novel arylbromide and bicyclic chemosensitizers against drug-resistant malaria parasites

Chouteau, Franck; Ramanitrahasimbola, David; Rasoanaivo, Philippe; Chibale, Kelly

doi:10.1016/j.bmcl.2005.04.033

Cited by 11 publications

(3 citation statements)

References 16 publications

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“…Several pathways to obtain the desired PBDE 3 and analogues are described in the literature, i.e. coupling of diphenyl iodyl salts with phenols (Luthe, Leonards, Reijerink, Liu, Johansen & Robertson, 2006, Marsh et al, 1999, coupling of arylboronic acids with phenols (Chouteau et al, 2005) ether molecule or its derivatives (Luthe, Leonards, Reijerink, Liu, Johansen & Robertson, 2006). PBDE 3 was synthesized by several methods independently.…”

Section: Synthesis Aspectsmentioning

confidence: 99%

Effects of fluoro substitution on 4-bromodiphenyl ether (PBDE 3)

Klösener

Swenson

Robertson

et al. 2008

Acta Crystallogr Sect B

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It is our hypothesis that fluoro substitution provides a powerful tool to modulate the desired characteristics and to increase the specificity of studies of structure-activity relationships. 4-Bromodiphenyl ether (PBDE 3) and its five corresponding monofluorinated analogues (F-PBDEs 3) have been synthesized and fully characterized (using (1)H, (13)C and (19)F NMR spectroscopy, and mass spectrometry). The accurate structure from X-ray crystal analysis was compared with iterative calculations using semi-empirical self-consistent field molecular-orbital (SCF-MO) models. The compounds studied were 4-bromodiphenyl ether (PBDE 3), the (13)C(6)-isotopically labeled PBDE 3 ((13)C(6)-PBDE 3) and 2-fluoro-4-bromodiphenyl ether (3-2F), 2'-fluoro-4-bromodiphenyl ether (3-2'F), 3-fluoro-4-bromodiphenyl ether (3-3F), 3'-fluoro-4-bromodiphenyl ether (3-3'F), and 4'-fluoro-4-bromodiphenyl ether (3-4'F). Solid-state intermolecular interactions for PBDE 3 and the F-PBDEs 3 isomers are dominated by weak C-H(F,Br)...pi and C-H...F interactions. The C-F bond lengths varied between 1.347 (2) and 1.362 (2) A, and the C4-Br bond length between 1.880 (3) and 1.904 (2) A. These bond lengths are correlated with electron-density differences, as determined by (13)C shifts, but not with the strength of the C-F couplings. The interior ring angles of ipso-fluoro substitution increased (121.9-124.0 degrees ) as a result of hyperconjugation, a phenomenon also predicted by the calculation models. An attraction between the vicinal fluoro and halo substituents (observed in fluoro substituted chlorobiphenyls) was not observed for the bromo substituted F-PBDEs. The influence of a fluoro substituent on the conformation was only observable in PBDEs with di-ortho substitution. Calculated and observed torsion angles showed a positive correlation with increasing van der Waals radii and/or the degree of substitution for mono- to tetra-fluoro, chloro, bromo and methyl substitutions in the ortho positions of diphenyl ether. These findings utilizing F-tagged analogues presented here may prove fundamental to the interpretation of the biological effects and toxicities of these persistent environmental pollutants.

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Section: Synthesis Aspectsmentioning

confidence: 99%

Effects of fluoro substitution on 4-bromodiphenyl ether (PBDE 3)

Klösener

Swenson

Robertson

et al. 2008

Acta Crystallogr Sect B

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“…The reactivity of 1 in the Suzuki‐Miyaura coupling reaction was first studied with phenyl boronic acid as model reagent, adopting the experimental conditions of Thiemann et al., but only starting material was recovered. Changing the solvent to THF, DMF or DMSO did not aid the formation of the desired product, despite the several reported examples of Suzuki‐Miyaura processes on bromo‐phenols and bromo‐anilines . Deprotonation of the phenol group of 1 (K 2 CO 3 was typically used) may be responsible for an intermediate hampering the catalytic cycle of the process.…”

Section: Resultsmentioning

confidence: 99%

Suzuki and Heck Processes for the Synthesis of New Anthraquinone‐Based Glycoconjugated Dyes

Calugi¹,

Bonanni²,

Corsi³

et al. 2018

ChemistrySelect

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Starting from a bromo‐anthraquinone dye, different aryl‐ and styril‐ derivates are obtained following Suzuki and Heck procedures. Bathochromic shifts are displayed for the products, if compared to the starting anthraquinone dye. Two of these dyes, coming from either the Suzuki and the Heck processes, have been glycosylated with a piperazinyl‐lactose derivative, so that two naturalized species are finally obtained. Therefore, the disperse chromophores were transformed in water soluble direct species. These kinds of dyes allow to avoid azo‐ structures, that are object of growing criticism in the European Union due to their environmental impact.

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“…7,19 It has been shown that in chloroquine-resistant malaria parasites, malagashanine stimulates the influx but reduces the efflux of chloroquine 20 and the alkaloid does not appear to be cytotoxic or cardiotoxic alone or in combination with chloroquine; some simplified analogues of malagashanine have also been evaluated. 21 A small clinical study has been carried out using chloroquine in combination of S. myrtoides stem bark (see below). Cryptolepine (7), an indoloquinoline alkaloid, is the main constituent of the West African climbing shrub Cryptolepis sanguinolenta.…”

Section: Indole and Indoloquinoline Alkaloidsmentioning

confidence: 99%