Synthesis of new optically pure tetrabromobenzotriazole derivatives via lipase-catalyzed transesterification

Wawro, Adam M.; Wielechowska, Monika; Bretner, Maria

doi:10.1016/j.molcatb.2012.10.013

Cited by 8 publications

(4 citation statements)

References 31 publications

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“…This phenomenon mainly stems from their high catalytic activity and thermal stability in organic solvents as well as wide substrates specificity toward xenobiotic substances. It is worth mentioning that in our previous synthetic campaigns the enzymatic method based on lipase catalysis was utilized to obtain optically pure CK2 inhibitors possessing both 4,5,6,7-tetrabromo-1H-benzotriazole (TBBt) [59,60] and TBBi [61] scaffolds. In this study, the biocatalytic approach allowed us to obtain final compounds with higher yields (58 to 88%) than when using convenient esterification conditions, while vinyl esters were used as acyl donors, instead of toxic and highly corrosive acyl chlorides.…”

Section: Chemistrymentioning

confidence: 99%

Synthesis of Novel Acyl Derivatives of 3-(4,5,6,7-Tetrabromo-1H-benzimidazol-1-yl)propan-1-ols—Intracellular TBBi-Based CK2 Inhibitors with Proapoptotic Properties

Chojnacki

Wińska

Karatsai

et al. 2021

IJMS

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Protein kinase CK2 has been considered as an attractive drug target for anti-cancer therapy. The synthesis of N-hydroxypropyl TBBi and 2MeTBBi derivatives as well as their respective esters was carried out by using chemoenzymatic methods. Concomitantly with kinetic studies toward recombinant CK2, the influence of the obtained compounds on the viability of two human breast carcinoma cell lines (MCF-7 and MDA-MB-231) was evaluated using MTT assay. Additionally, an intracellular inhibition of CK2 as well as an induction of apoptosis in the examined cells after the treatment with the most active compounds were studied by Western blot analysis, phase-contrast microscopy and flow cytometry method. The results of the MTT test revealed potent cytotoxic activities for most of the newly synthesized compounds (EC50 4.90 to 32.77 µM), corresponding to their solubility in biological media. We concluded that derivatives with the methyl group decrease the viability of both cell lines more efficiently than their non-methylated analogs. Furthermore, inhibition of CK2 in breast cancer cells treated with the tested compounds at the concentrations equal to their EC50 values correlates well with their lipophilicity since derivatives with higher values of logP are more potent intracellular inhibitors of CK2 with better proapoptotic properties than their parental hydroxyl compounds.

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Section: Chemistrymentioning

confidence: 99%

Synthesis of Novel Acyl Derivatives of 3-(4,5,6,7-Tetrabromo-1H-benzimidazol-1-yl)propan-1-ols—Intracellular TBBi-Based CK2 Inhibitors with Proapoptotic Properties

Chojnacki

Wińska

Karatsai

et al. 2021

IJMS

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“…Based on these considerations and taking as reference the hydroxyalkyl derivatives synthesized by Nadja-Bernatowicz [199] and Makowska [203], the group developed a new synthetic approach to isolate enantiopure hydroxyalkyl derivatives of TBBt (69aec, Fig. 49), obtaining optically active compounds endowed with enantioselectivity factor (E > 200) [206]. These molecules, potentially CK2 inhibitors, might be used to synthesize new optically pure TBBt derivatives.…”

Section: Benzotriazole As Protein Kinase Ck2 Inhibitormentioning

confidence: 99%

Benzotriazole: An overview on its versatile biological behavior

Briguglio

Piras

Corona

et al. 2015

European Journal of Medicinal Chemistry

161

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Discovered in late 1960, azoles are heterocyclic compounds class which constitute the largest group of available antifungal drugs. Particularly, the imidazole ring is the chemical component that confers activity to azoles. Triazoles are obtained by a slight modification of this ring and similar or improved activities as well as less adverse effects are reported for triazole derivatives. Consequently, it is not surprising that benzimidazole/benzotriazole derivatives have been found to be biologically active. Since benzimidazole has been widely investigated, this review is focused on defining the place of benzotriazole derivatives in biomedical research, highlighting their versatile biological properties, the mode of action and Structure Activity Relationship (SAR) studies for a variety of antimicrobial, antiparasitic, and even antitumor, choleretic, cholesterol-lowering agents.

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“…Researches revealed that its four bromine atoms in benzotriazole ring were essential requirement for the inhibitory activity [28]. Recently, several new TBB derivatives have been developed and employed to inhibit CK2 in various proteins with important metabolic functions [29,30]. For example, the introduction of a propanol moiety into TBB at 1-position (compound 1b) resulted in a better inhibition with half maximal inhibitory concentration (IC 50 value) of 0.32 µg/mL in comparison to the parental TBB (IC 50 =0.56 µg/mL).…”

Section: Anticancer Benzotriazolesmentioning

confidence: 99%

Recent Development of Benzotriazole-based Medicinal Drugs

Ren¹

2014

Med chem

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The inhibition of kinases is one of the most important pathways to treat cancers attributing to the significant roles of kinases in cell multiplication [24]. The special structure of benzotriazole derivatives could readily bind with different kinases via multiple non-covalent forces such as hydrogen bonds, coordination, ion-dipole, cation-π, π-π stacking, hydrophobic effect and van der Waals force, thus effectively inhibiting the activity of various kinases including protein kinases CK2 and CHK1, histone deacetylases and focal adhesion kinase and so on.

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Synthesis of new optically pure tetrabromobenzotriazole derivatives via lipase-catalyzed transesterification

Cited by 8 publications

References 31 publications

Synthesis of Novel Acyl Derivatives of 3-(4,5,6,7-Tetrabromo-1H-benzimidazol-1-yl)propan-1-ols—Intracellular TBBi-Based CK2 Inhibitors with Proapoptotic Properties

Synthesis of Novel Acyl Derivatives of 3-(4,5,6,7-Tetrabromo-1H-benzimidazol-1-yl)propan-1-ols—Intracellular TBBi-Based CK2 Inhibitors with Proapoptotic Properties

Benzotriazole: An overview on its versatile biological behavior

Recent Development of Benzotriazole-based Medicinal Drugs

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