Aflatoxin B1–Formamidopyrimidine DNA Adducts: Relationships between Structures, Free Energies, and Melting Temperatures

Klvaňa, Martin; Bren, Urban

doi:10.3390/molecules24010150

Cited by 28 publications

(15 citation statements)

References 137 publications

(219 reference statements)

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“…Each MD simulation afforded 1000 snapshots (using 100 ps intervals) of each compound in different environments which were used for calculating average electrostatic and VdW energies. Energies were simply averaged for the ligand-free simulation (2 sets separately for compounds 1 and 2 ), while ligand bound potential energies were initially weighted according to Equation (2) and subsequently used in the general LIE Equation (1) ( Table 2 ) [ 35 , 36 , 48 ]. The employed method was reported as suitable for calculation of ligand binding free energy, compared to MM/PBSA and reported to produce relevant results even with shorter simulation times when compared to alternative methodologies [ 49 ].…”

Section: Methodsmentioning

confidence: 99%

Ensemble Docking Coupled to Linear Interaction Energy Calculations for Identification of Coronavirus Main Protease (3CLpro) Non-Covalent Small-Molecule Inhibitors

2020

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SARS-CoV-2, or severe acute respiratory syndrome coronavirus 2, represents a new strain of Coronaviridae. In the closing 2019 to early 2020 months, the virus caused a global pandemic of COVID-19 disease. We performed a virtual screening study in order to identify potential inhibitors of the SARS-CoV-2 main viral protease (3CLpro or Mpro). For this purpose, we developed a novel approach using ensemble docking high-throughput virtual screening directly coupled with subsequent Linear Interaction Energy (LIE) calculations to maximize the conformational space sampling and to assess the binding affinity of identified inhibitors. A large database of small commercial compounds was prepared, and top-scoring hits were identified with two compounds singled out, namely 1-[(R)-2-(1,3-benzimidazol-2-yl)-1-pyrrolidinyl]-2-(4-methyl-1,4-diazepan-1-yl)-1-ethanone and [({(S)-1-[(1H-indol-2-yl)methyl]-3-pyrrolidinyl}methyl)amino](5-methyl-2H-pyrazol-3-yl)formaldehyde. Moreover, we obtained a favorable binding free energy of the identified compounds, and using contact analysis we confirmed their stable binding modes in the 3CLpro active site. These compounds will facilitate further 3CLpro inhibitor design.

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Section: Methodsmentioning

confidence: 99%

Ensemble Docking Coupled to Linear Interaction Energy Calculations for Identification of Coronavirus Main Protease (3CLpro) Non-Covalent Small-Molecule Inhibitors

2020

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“…In addition, aflatoxins were reported to cause lung [4] and skin [5] occupational cancers via inhalation and direct contact, respectively. In fact, chronic exposure to aflatoxins causes a range of other severe diseases, including immunosuppression, teratogenicity, mutagenicity, cytotoxicity, and estrogenic effects in mammalians [6]. Moreover, aflatoxins are believed to be involved in nutritional disorders, such as kwashiorkor and growth faltering, probably by interfering with the absorption of micronutrients (e.g., zinc, iron, and vitamins), protein synthesis, and metabolic enzyme activities [2,7].…”

Section: Chronic Diseases Caused By Aflatoxinsmentioning

confidence: 99%

“…AFBO has long been considered as the ultimate metabolite responsible for the genotoxic effects of AFB1 as well as other aflatoxins bearing a double bond between carbons C 8 and C 9 done in the furan ring [6,21]. The mechanisms of toxicity mediated by this AFB1 reactive metabolite are the best understood and have been extensively reviewed [17,[22][23][24].…”

Section: Afbo-mediated Genotoxicitymentioning

confidence: 99%

Chronic and Acute Toxicities of Aflatoxins: Mechanisms of Action

Benkerroum

2020

IJERPH

354

214

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There are presently more than 18 known aflatoxins most of which have been insufficiently studied for their incidence, health-risk, and mechanisms of toxicity to allow effective intervention and control means that would significantly and sustainably reduce their incidence and adverse effects on health and economy. Among these, aflatoxin B1 (AFB1) has been by far the most studied; yet, many aspects of the range and mechanisms of the diseases it causes remain to be elucidated. Its mutagenicity, tumorigenicity, and carcinogenicity—which are the best known—still suffer from limitations regarding the relative contribution of the oxidative stress and the reactive epoxide derivative (Aflatoxin-exo 8,9-epoxide) in the induction of the diseases, as well as its metabolic and synthesis pathways. Additionally, despite the well-established additive effects for carcinogenicity between AFB1 and other risk factors, e.g., hepatitis viruses B and C, and the hepatotoxic algal microcystins, the mechanisms of this synergy remain unclear. This study reviews the most recent advances in the field of the mechanisms of toxicity of aflatoxins and the adverse health effects that they cause in humans and animals.

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“…Contrastingly, compound 4 displayed weak cytotoxicity in SGC-7901 and K562, with IC 50 values of 26.2 ± 0.4 and 21.9 ± 0.3 μM, respectively. By comparison, the cytotoxicity in BEL-7401 and SGC-7901 was slightly enhanced when the double bond between C-9 and C-10 in compound 1 was oxidized to the epoxy group in compound 6 , which could be due to the highly genotoxic effect of the epoxy group [37,38].…”

Section: Resultsmentioning

confidence: 99%

Polyacetylenes from the Roots of Swietenia macrophylla King

Wang

Chen

et al. 2019

Molecules

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A phytochemical investigation of the roots of Swietenia macrophylla led to the isolation of seven polyacetylenes, including five new compounds (15) and two known ones (67). Their structures were elucidated by extensive spectroscopic analysis and detailed comparison with reported data. All the isolates were tested for their cytotoxicity against the human hepatocellular carcinoma cell line BEL-7402, human myeloid leukemia cell line K562, and human gastric carcinoma cell line SGC-7901. Compounds 1 and 6 showed moderate cytotoxicity against the above three human cancer cell lines with IC50 values ranging from 14.3 to 45.4 μM. Compound 4 displayed cytotoxicity against the K562 and SGC-7901 cancer cell lines with IC50 values of 26.2 ± 0.4 and 21.9 ± 0.3 μM, respectively.

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Aflatoxin B1–Formamidopyrimidine DNA Adducts: Relationships between Structures, Free Energies, and Melting Temperatures

Abstract: Thermal stabilities of DNA duplexes containing Gua (g), α- (a) or β-anomer of formamidopyrimidine-N7-9-hydroxy-aflatoxin B1 (b) differ markedly (Tm: a Show more

Cited by 28 publications

References 137 publications

Ensemble Docking Coupled to Linear Interaction Energy Calculations for Identification of Coronavirus Main Protease (3CLpro) Non-Covalent Small-Molecule Inhibitors

Ensemble Docking Coupled to Linear Interaction Energy Calculations for Identification of Coronavirus Main Protease (3CLpro) Non-Covalent Small-Molecule Inhibitors

Chronic and Acute Toxicities of Aflatoxins: Mechanisms of Action

Polyacetylenes from the Roots of Swietenia macrophylla King

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