Synthesis and cytotoxicity of some d-mannose click conjugates with aminobenzoic acid derivatives

Hradilová, Ludmila; Poláková, Monika; Dvořáková, Barbora; Hajdúch, Marián; Petruš, Ladislav

doi:10.1016/j.carres.2012.08.001

Cited by 18 publications

(14 citation statements)

References 60 publications

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“…[26] However, upon deprotection of the DMTr group with acetic acid, the anthraniloyl moiety partially migrates from 2’-position to 3’-position to give an inseparable mixture of compounds 3 and 4 (Scheme 1) in a ratio 5:1 and in overall 79% yield. This isomerization was observed with MANT-nucleotides as well.…”

Section: Resultsmentioning

confidence: 99%

Design and Synthesis of Fluorescent Acyclic Nucleoside Phosphonates as Potent Inhibitors of Bacterial Adenylate Cyclases

et al. 2016

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Bordetella pertussis adenylate cyclase toxin (ACT) and Bacillus anthracis edema factor (EF) are key virulence factors with adenylate cyclase (AC) activity that substantially contribute to the pathogenesis of whooping cough and anthrax, respectively. There is an urgent need to develop potent and selective inhibitors of bacterial ACs with prospects for development of potential antibacterial therapeutics and to study their molecular interactions with the target enzymes. Novel fluorescent 5-chloroanthraniloyl-substituted acyclic nucleoside phosphonates (Cl-ANT-ANPs) were designed and synthesized in the form of their diphosphates (Cl-ANT-ANPpp) as competitive ACT and EF inhibitors with submicromolar potency (IC50 values 11 – 622 nM). Fluorescence experiments indicated that Cl-ANT-ANPpp analogues bind to the ACT active site and docking studies suggested that the Cl-ANT group interacts with Phe306 and Leu60. Interestingly, the increase of direct fluorescence with Cl-ANT-ANPpp having an ester linker was strictly CaM-dependent, whereas Cl-ANT-ANPpp analogues with an amide linker, upon binding to ACT, increased the fluorescence even in the absence of CaM. Such a dependence of binding on structural modification could be exploited in the future design of potent inhibitors of bacterial ACs. Furthermore, one Cl-ANT-ANP in the form of a bisamidate prodrug was able to inhibit B. pertussis ACT activity in macrophage cells with IC50 = 12 µM.

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Section: Resultsmentioning

confidence: 99%

Design and Synthesis of Fluorescent Acyclic Nucleoside Phosphonates as Potent Inhibitors of Bacterial Adenylate Cyclases

et al. 2016

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“…In addition to PABA "non-imine" cytotoxic derivatives [1,5,12,44], Farooq et al [18] discovered N-alkylisatin-3-iminobenzoic acids, i.e., Schiff bases of substituted isatin and PABA, as potential cytotoxic/antileukemic agents with IC 50 for human normal as well as cancer cell lines comparable to our the most active molecules. Thus, the formation of Schiff bases could convert non-toxic PABA to moderate cytotoxic agents, depending on the carbonyl compound used.…”

Section: Cytotoxicitymentioning

confidence: 96%

4-Aminobenzoic Acid Derivatives: Converting Folate Precursor to Antimicrobial and Cytotoxic Agents

et al. 2019

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4-aminobenzoic acid (PABA), an essential nutrient for many human pathogens, but dispensable for humans, and its derivatives have exhibited various biological activities. In this study, we combined two pharmacophores using a molecular hybridization approach: this vitamin-like molecule and various aromatic aldehydes, including salicylaldehydes and 5-nitrofurfural, via imine bond in one-step reaction. Resulting Schiff bases were screened as potential antimicrobial and cytotoxic agents. The simple chemical modification of non-toxic PABA resulted in constitution of antibacterial activity including inhibition of methicillin-resistant Staphylococcus aureus (minimum inhibitory concentrations, MIC, from 15.62 µM), moderate antimycobacterial activity (MIC ≥ 62.5 µM) and potent broad-spectrum antifungal properties (MIC of ≥ 7.81 µM). Some of the Schiff bases also exhibited notable cytotoxicity for cancer HepG2 cell line (IC 50 ≥ 15.0 µM). Regarding aldehyde used for the derivatization of PABA, it is possible to tune up the particular activities and obtain derivatives with promising bioactivities.

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“…Final deacetylation could afford the target compound 8. However, attempt to deprotection of the acetyl groups of 5 using various reagents such as (i) NaOMe/MeOH [28], (ii) K 2 CO 3 /MeOH [29], (iii) Et 3 N/MeOH/H 2 O [30], (iv) NH 4 OH/ MeOH [31] failed to give the desired compounds; all of compounds underwent decomposition or no reaction under such conditions. Nevertheless, the deprotections were achieved via treating the compounds in methanol with dibutyltin oxide [32] under reflux condition, furnishing the target compounds 6a-6f in excellent yield.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Design, synthesis and biological evaluation of gentiopicroside derivatives as potential antiviral inhibitors

Yang

Sun

et al. 2017

European Journal of Medicinal Chemistry

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Based on classical drug design theory, a novel series of gentiopicroside derivatives was designed and synthesized. All synthesized compounds were then biologically evaluated for their inhibition of influenza virus and anti-HCV activity in vitro. Some of the gentiopicroside derivatives, such as 11a, 13d and 16 showed interesting anti-influenza virus activity with IC at 39.5 μM, 45.2 μM and 44.0 μM, respectively. However, no significant anti-HCV activity was found for all of gentiopicroside derivatives. The preliminary results indicate that modification of the sugar moiety on gentiopicroside was helpful for enhancing the anti-influenza activities. Our works demonstrate the importance of secoiridoid natural products as new leads in the development of potential antiviral inhibitors.

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Synthesis and cytotoxicity of some d-mannose click conjugates with aminobenzoic acid derivatives

Cited by 18 publications

References 60 publications

Design and Synthesis of Fluorescent Acyclic Nucleoside Phosphonates as Potent Inhibitors of Bacterial Adenylate Cyclases

Design and Synthesis of Fluorescent Acyclic Nucleoside Phosphonates as Potent Inhibitors of Bacterial Adenylate Cyclases

4-Aminobenzoic Acid Derivatives: Converting Folate Precursor to Antimicrobial and Cytotoxic Agents

Design, synthesis and biological evaluation of gentiopicroside derivatives as potential antiviral inhibitors

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