What Is the Structure of the Antitubercular Natural Product Eucapsitrione?

Pullella, Glenn A.; Wild, Duncan A.; Nealon, Gareth L.; Elyashberg, Mikhail E.; Piggott, Matthew

doi:10.1021/acs.joc.7b00863

Cited by 13 publications

(8 citation statements)

References 95 publications

(154 reference statements)

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“…The mechanism of these antibacterial agents involves enhanced ROS generation and is followed by apoptotic cell death [6,7]. A number of compounds with a 1,4-naphthoquinone moiety can activate noticeable biological inhibitions such as antimicrobial [8], anticancer [9], antitubercular [10], antimalarial [11] and trypanocidal [12] activities. Due to the ability to generate ROS, naphthoquinone analogues are extremely cytotoxic to the infected cells and can restrict cellular enzymes, which are responsible for apoptosis and cell growth [13].…”

Section: Introductionmentioning

confidence: 99%

1,4-Naphthoquinone Analogues: Potent Antibacterial Agents and Mode of Action Evaluation

et al. 2019

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1,4-Naphthoquinones have antibacterial activity and are a promising new class of compound that can be used to treat bacterial infections. The goal was to improve effective antibacterial agents; therefore, we synthesized a new class of naphthoquinone hybrids, which contain phenylamino-phenylthio moieties as significant counterparts. Compound 4 was modified as a substituted aryl amide moiety, which enhanced the antibacterial activity of earlier compounds 3 and 4. In this study, five bacterial strains Staphylococcus aureus (S. aureus), Listeria monocytogenes (L. monocytogenes), Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa) and Klebsiella pneumoniae (K. pneumoniae) were used to evaluate the antibacterial potency of synthesized naphthoquinones using the minimal inhibitory concentration (MIC) method. Most of the studied naphthoquinones demonstrated major antibacterial activity with a MIC of 15.6 µg/mL–500 µg/mL. Selected compounds (5a, 5f and 5x) were studied for the mode of action, using intracellular ROS generation, determination of apoptosis by the Annexin V-FITC/PI assay, a bactericidal kinetic study and in silico molecular modelling. Additionally, the redox potentials of the specified compounds were confirmed by cyclic voltammetry (CV).

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Section: Introductionmentioning

confidence: 99%

1,4-Naphthoquinone Analogues: Potent Antibacterial Agents and Mode of Action Evaluation

et al. 2019

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“…[4,5] Notably,1 ,4-naphthoquinonesg raftedw ith an amino or substituted amino group at the 2-position have been potential candidates in medical and biological applications. Furthermore, recent researchh as demonstrated that these molecules exhibit antitubercular, [6] antimalarial, [7] trypanocidal, [8] anticancer, [9] and antimicrobial [10] activities.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Anticancer Evaluation of 1,4‐Naphthoquinone Derivatives Containing a Phenylaminosulfanyl Moiety

et al. 2019

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1,4‐Naphthoquinones are exceptional building blocks in organic synthesis and have been used to synthesize several well‐known pharmaceutically active agents. Herein we report the synthesis, structural characterization, and biological evaluation of new phenylaminosulfanyl‐1,4‐naphthoquinone derivatives. We evaluated the cytotoxic activity of the synthesized compounds against three human cancer cell lines: A549, HeLa, and MCF‐7. Most of the synthesized compounds displayed potent cytotoxic activity. Specifically, compounds 5 e [3,5‐dichloro‐N‐(4‐((4‐((1,4‐dioxo‐3‐(phenylthio)‐1,4‐dihydronaphthalen‐2‐yl)amino)phenyl)sulfonyl)phenyl)benzamide], 5 f [N‐(4‐((4‐((1,4‐dioxo‐3‐(phenylthio)‐1,4‐dihydronaphthalen‐2‐yl)amino)phenyl)sulfonyl)phenyl)‐3,5‐dinitrobenzamide], and 5 p [N‐(4‐((4‐((1,4‐dioxo‐3‐(phenylthio)‐1,4‐dihydronaphthalen‐2‐yl)amino)phenyl)sulfonyl)phenyl)thiophene‐2‐carboxamide] showed remarkable cytotoxic activity. The synthesized compounds showed low toxicity in normal human kidney HEK293 cells. The cytotoxic mechanism of compounds 5 e, 5 f, and 5 p was explored in MCF‐7 cells. The results confirmed that these three compounds induce apoptosis and arrest the cell cycle at the G1 phase. In addition, compounds 5 e, 5 f, and 5 p were found to induce apoptosis via upregulation of caspase‐3 and caspase‐7 proteins as well as by upregulation of the gene expression levels of caspases‐3 and ‐7. Our findings demonstrate that compounds 5 e, 5 f, and 5 p could be potent agents against a number of cancer types.

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“…[7,8] 1,4-Naphthoquinones and its related compounds are well-established for irreversible complexation during ROS generation in proteins, which leads to loss of protein function. [9] Due to these properties, 1,4-naphthoquinone derivatives exhibit biological properties such as antimicrobial, [10] antimalarial, [11] antitubercular, [12] anticancer, [13] and trypanocidal [14] activities.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Antimicrobial Evaluation of 1,4‐Naphthoquinone Derivatives as Potential Antibacterial Agents

Ravichandiran

Masłyk

Sheet³

et al. 2019

ChemistryOpen

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1,4‐Naphthoquinones are an important class of compounds present in a number of natural products. In this study, a new series of 1,4‐naphthoquinone derivatives were synthesized. All the synthesized compounds were tested for in vitro antimicrobial activity. In this present investigation, two Gram‐positive and five Gram‐negative bacterial strains and one pathogenic yeast strain were used to determine the antibacterial activity. Naphthoquinones tested for its antibacterial potencies, among seven of them displayed better antimicrobial activity against Staphylococcus aureus ( S. aureus ; 30–70 μg/mL). Some of the tested compounds showed moderate to low antimicrobial activity against Pseudomonas aeruginosa ( P. aeruginosa ) and Salmonella bongori ( S. bongori ; 70–150 μg/mL). In addition, most active compounds against S. aureus were evaluated for toxicity to human blood cells using a hemolysis assay. For better understanding, reactive oxygen species (ROS) generation, time‐kill kinetic study, and apoptosis, necrosis responses were investigated for three representative compounds.

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What Is the Structure of the Antitubercular Natural Product Eucapsitrione?

Cited by 13 publications

References 95 publications

1,4-Naphthoquinone Analogues: Potent Antibacterial Agents and Mode of Action Evaluation

1,4-Naphthoquinone Analogues: Potent Antibacterial Agents and Mode of Action Evaluation

Synthesis and Anticancer Evaluation of 1,4‐Naphthoquinone Derivatives Containing a Phenylaminosulfanyl Moiety

Synthesis and Antimicrobial Evaluation of 1,4‐Naphthoquinone Derivatives as Potential Antibacterial Agents

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