Chalcone–Benzoxaborole Hybrid Molecules as Potent Antitrypanosomal Agents

Qiao, Zhitao; Wang, Qi; Zhang, Fenglong; Wang, Zhongli; Bowling, Tana; Nare, Bakela; Jacobs, Robert T.; Zhang, Jiong; Ding, Dazhong; Liu, Yangang; Zhou, Huchen

doi:10.1021/jm2012408

Cited by 83 publications

(69 citation statements)

References 23 publications

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“…For instance, 5-fluoro-and 5-chloro-1,3-dihydro-2,1-benzoxaborole (referred to as AN2690 and AN2718, respectively) were identified as potent antifungal agents against infection of the nails (dermatophytic onychomycosis). 11 Other benzoxaboroles are also effective against other important human diseases, including human African trypanosomiasis (HAT, known as sleeping sickness), 12 malaria, 13 and some liver dysfunctions. 14 Recent intensive efforts have resulted in the preparation of over 6000 benzoxaborole derivatives.…”

Section: ■ Introductionmentioning

confidence: 99%

Benzosiloxaboroles: Silicon Benzoxaborole Congeners with Improved Lewis Acidity, High Diol Affinity, and Potent Bioactivity

Brzozowska¹,

Ćwik²,

Durka³

et al. 2015

Organometallics

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The synthesis and physicochemical properties of benzosiloxaboroles, the silicon analogues of an important class of heterocyclic compoundsbenzoxaborolesis presented. They were prepared by halogen−lithium exchange reactions of (2-bromophenyl)boronates with n-BuLi followed by the silylation or boronation of (2-lithiophenyl)dimethylsilanes. The cyclization of the resulting 2-(dimethylsilyl)phenylboronates apparently occurs through intramolecular dehydrogenative cyclization reaction in the presence of water. Unlike the case for benzosiloxaborole, the formation of its analogue containing a thiophene ring is thermodynamically unfavorable, which was confirmed by theoretical calculations. The presence of a B−O−Si linkage results in increased Lewis acidity with respect to the analogous benzoxaboroles. The acidity is strongly enhanced by fluorination or introduction of phenyl groups at the silicon atom. Selected compounds show good antifungal activity, and thus they are potential small-molecule therapeutic agents. They can also serve as effective receptors for biologically relevant diols under neutral pH conditions.

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Section: ■ Introductionmentioning

confidence: 99%

Benzosiloxaboroles: Silicon Benzoxaborole Congeners with Improved Lewis Acidity, High Diol Affinity, and Potent Bioactivity

Brzozowska¹,

Ćwik²,

Durka³

et al. 2015

Organometallics

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“…Of the boron-containing compounds that are currently in pharmaceutical development programs, boronic acids [1,2], boronate esters [3,4], benzoxaboroles [5,6], and oxazaborolidines [7,8] are frequently used boron functional groups. Having an empty p-orbital on the trivalent boron atom, these analogs interact with their targets to form tetrahedral intermediates.…”

Section: Abstract: Peptide; Organotrifluoroborate; Potassium Trifluormentioning

confidence: 99%

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mentioning

confidence: 99%

Potassium {4-[(3S,6S,9S)-3,6-dibenzyl-9-isopropyl-4,7,10-trioxo-11–oxa-2,5,8-triazadodecyl]phenyl}trifluoroborate

Tsai

Lin

Hsieh

et al. 2014

Molbank

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[5,6], and oxazaborolidines [7,8] are frequently used boron functional groups. Having an empty p-orbital on the trivalent boron atom, these analogs interact with their targets to form tetrahedral intermediates. Organotrifluoroborates, on the other hand, are seldom considered in biological applications due to their lack of an empty p-orbital. Srebnik and coworkers, the first group to investigate the biological activity of a series of aryl organotrifluoroborates in enzyme-inhibition assays, reported that aryl potassium trifluoroborates were much more potent than the corresponding boronic acids against α-chymotrypsin and trypsin [9,10]. The toxicological profile of organotrifluoroborates were also investigated by Oliveira and co-workers, who showed that thiophene-3-trifluoroborate exhibits minimal toxicity in a mouse model, and concluded that this class of compounds is suitable for further development as pharmacologically active agents [11]. Despite their promising biological studies, the reported studies of organotrifluoroborates OPEN ACCESS

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“…Nevertheless, hybrid molecules incorporating the chalcone moiety are emerging as promising leads for targeting Leishmania and Trypanosoma species [8e11]. For example, the chalcone-benzoxaborole hybrid 2 gave 100% mouse survival rate and complete elimination of parasites in a T. b. brucei murine model [9].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and antitrypanosomal activities of novel pyridylchalcones

Bhambra

Ruparelia

Tan

et al. 2017

European Journal of Medicinal Chemistry

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a b s t r a c tA library of novel pyridylchalcones were synthesised and screened against Trypanosoma brucei rhodesiense. Eight were shown to have good activity with the most potent 8 having an IC 50 value of 0.29 mM.Cytotoxicity testing with human KB cells showed a good selectivity profile for this compound with a selectivity index of 47. Little activity was seen when the library was tested against Leishmania donovani. In conclusion, pyridylchalcones are promising leads in the development of novel compounds for the treatment of human African trypanosomiasis (HAT).

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Chalcone–Benzoxaborole Hybrid Molecules as Potent Antitrypanosomal Agents

Cited by 83 publications

References 23 publications

Benzosiloxaboroles: Silicon Benzoxaborole Congeners with Improved Lewis Acidity, High Diol Affinity, and Potent Bioactivity

Benzosiloxaboroles: Silicon Benzoxaborole Congeners with Improved Lewis Acidity, High Diol Affinity, and Potent Bioactivity

Potassium {4-[(3S,6S,9S)-3,6-dibenzyl-9-isopropyl-4,7,10-trioxo-11–oxa-2,5,8-triazadodecyl]phenyl}trifluoroborate

Synthesis and antitrypanosomal activities of novel pyridylchalcones

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