Artonin I inhibits multidrug resistance in <i>Staphylococcus aureus</i>
 and potentiates the action of inactive antibiotics <i>in vitro</i>

Farooq, Saba; Wahab, Atia‐tul; Fozing, Christian D.; Rahman, Atta Ur; Choudhary, M. Iqbal

doi:10.1111/jam.12595

Cited by 37 publications

(20 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is noteworthy that S. aureus (ATCC® 25923) is a MSSA and a biofilm forming strain. Furthermore, ultrastructural changes showed that the flavonoid artonin I was able to induce destruction through cell membrane damage and abnormal division pattern alteration on MDR- S. aureus strains [48]. Probably, the flavonoids detected in HEJ30, HEJ50, HEJ70, HES30, HES50, and HES70 possess a similar mode of action against S. aureus (ATCC® 6538), S. aureus (ATCC® 29213), and the five MRSA clinical strains tested.…”

Section: Resultsmentioning

confidence: 99%

Kalanchoe brasiliensisCambess., a Promising Natural Source of Antioxidant and Antibiotic Agents against Multidrug-Resistant Pathogens for the Treatment ofSalmonellaGastroenteritis

Mayorga

Costa

Silva

et al. 2019

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Kalanchoe brasiliensis Cambess. is a native Brazilian plant popularly known as “saião”, and the juice of its fresh leaves is traditionally used to treat several disorders, including inflammatory and infectious processes such as dysentery. The goals of this study were to characterize the phytochemical composition and investigate the antioxidant activity, the antibiotic effect, and the mode of action against Salmonella of the hydroethanolic extracts from K. brasiliensis leaves collected in the summer and spring Brazilian seasons. These extracts had their chemical composition established by high-performance liquid chromatography with diode-array detection. Total phenolic and flavonoid contents were spectrophotometrically determined. 2,2-Diphenyl-1-picryl-hydrazyl radical scavenging, phosphomolybdenum reducing power and β-carotene bleaching assays were carried out to evaluate the antioxidant capacity. Antibiotic potential was assessed by minimal inhibitory concentration against 8 bacterial ATCC® and 5 methicillin-resistant Staphylococcus aureus and 5 Salmonella clinical strains. The mode of action was investigated by time-kill, bacterial cell viability, and leakage of compounds absorbing at 280 nm assays against Salmonella. Chromatographic profile and UV spectrum analyses suggested the significant presence of flavonoid type patuletin and eupafolin derivatives, and no difference between both periods of collection was noted. Significant amounts of total phenolic and flavonoid contents and a promising antioxidant capacity were observed. Hydroethanolic extracts (70%, summer and spring) were the most active against the tested Gram-positive and Gram-negative bacterial strains, showing the bacteriostatic action of 5000 μg/mL. Time-kill data demonstrated that these extracts were able to reduce the Salmonella growth rate. Cell number was reduced with release of the bacterial content. Together, these results suggest that K. brasiliensis is a natural source of antioxidant and antibacterial agents that can be applied in the research and development of new antibiotics for the treatment of Salmonella gastroenteritis because they are able to interfere in the Salmonella growth, probably due to cell membrane damage.

show abstract

Section: Resultsmentioning

confidence: 99%

Kalanchoe brasiliensisCambess., a Promising Natural Source of Antioxidant and Antibiotic Agents against Multidrug-Resistant Pathogens for the Treatment ofSalmonellaGastroenteritis

Mayorga

Costa

Silva

et al. 2019

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

show abstract

“…A recent analysis of drugs approved by the USA FDA drugs has again come to the conclusion both that natural products and their derivatives have both played a key role in the past and are likely to be a productive way forward in the future, and that appropriate investment from private and public sectors is justified. [168] Certainly, small molecules, and many of them related to natural products, offer interesting opportunities for the identification of short term solutions using resistance reversal agents [124,169] and resistance breakers; an example is artonin 10 (vide supra). [170] Notwithstanding the opportunities for the discovery of new natural products Gram-negatives and superior pharmacokinetic profiles when compared to colistin; this was achieved by a "classical" SAR study in which three key components of the polymixin framework were systematically modified and evaluated in detail.…”

Section: Discussionmentioning

confidence: 99%

“…[122,123] Artonin I 10 has been reported to be an efflux pump inhibitor, to inhibit multidrug resistance in S. aureus and, when used in combination with existing antibiotics, to lower their MIC values. [124] Such "helper" systems offer the possibility of extending the lifetime of existing clinically effective drugs.…”

Section: Opportunities For Natural Products In Antibiotic Drug Discoverymentioning

confidence: 99%

Natural Products as a Source for Novel Antibiotics

Moloney

2016

Trends in Pharmacological Sciences

248

163

View full text Add to dashboard Cite

Natural products have historically been of crucial importance in the identification and development of antibacterial agents. Interest in these systems has waned in recent years, but the rapid emergence of resistant bacterial strains has forced their re-evaluation as a route to identify novel chemical skeletons with antibacterial activity for elaboration in drug development. This overview examines the current situation, highlights new natural product systems which have been found, together with re-examination of some old ones, and new technologies for their identification. While natural products certainly have the potential to re-emerge as a key start-point in antibacterial drug discovery, reports of new or reinvestigated structures need to be supported with sufficient quality chemical (solubility, stability), biochemical (including toxicity in particular, along with target information) and microbiological [minimum inhibitory concentration (MIC) and resistance frequency] validation data to assist in the identification of promising hit structures and to avoid wasted effort from trawling over already cultivated territory. This is particularly important in a resource-limited research environment.

show abstract

“…Meanwhile, to determine the kinetic values of diene 3a, reactions were performed with 3a (3.5, 7.5, 15, 31.25, 62.5, 125, 250, and 500 µm) and the saturating 2 (1.0 mm) at pH 8.5 and 50°C for 5 min in a total volume of 100 µL that contained 820 nm MaDA. To determine the kinetic values of diene 3b, reactions were performed with 3b (5,10,20,40,80,100,250, and 500 µm) and the saturating 2 (1.0 mm) at pH 8.5 and 50°C for 5 min in a total volume of 100 µL that contained 34 nm MaDA. Aliquots were quenched with 100 µL of ice-cold MeOH and centrifuged at 15 000g for 30 min.…”

Section: Methodsmentioning

confidence: 99%

“…[ 19 ] This natural product shows potent phosphodiesterase I inhibitory activity [ 19 ] and inhibits multidrug resistance in Staphylococcus aureus . [ 20 ] To our knowledge, no total synthesis of artonin I has been reported yet. Similar with the proposed biosynthetic pathway of other Diels–Alder type natural products in Morus plants, [ 21 ] the enzyme‐catalyzed oxidation (or dehydrogenation) and Diels–Alder reaction were proposed as the final two key steps in the biosynthesis of artonin I by exogenous feeding of diene precursor in the Morus alba cell cultures.…”

Section: Introductionmentioning

confidence: 99%

Chemoenzymatic Total Syntheses of Artonin I with an Intermolecular Diels–Alderase

Liu

Yang

Gao

et al. 2020

Biotechnology Journal

View full text Add to dashboard Cite

Diels–Alder reaction is one of the most important transformations used in organic synthesis, with the ability to construct two new CC bonds and up to four chiral centers simultaneously. However, the biggest synthetic challenge in Diels–Alder reaction lies in controlling its regio‐, diastereo‐, and enantioselectivity. Using Stille cross‐coupling and enzymatic Diels–Alder reaction as the key steps, the first chemoenzymatic total synthesis of artonin I is achieved in 30% overall yield over only seven steps. This enzymatic Diels–Alder reaction catalyzed by MaDA is featured with excellent endo‐ and enantioselectivity and high catalytic efficiency (kcat/KM = 362 ± 54 mm−1 s−1). These successful chemoenzymatic total syntheses of artonin I and dideoxyartonin I demonstrated the remarkable potential of the intermolecular Diels–Alderase MaDA in biocatalysis.

show abstract

Artonin I inhibits multidrug resistance in Staphylococcus aureus and potentiates the action of inactive antibiotics in vitro

Abstract: Artonin I can be developed as potential antimicrobial and resistance reversal agent.

Cited by 37 publications

References 36 publications

Kalanchoe brasiliensisCambess., a Promising Natural Source of Antioxidant and Antibiotic Agents against Multidrug-Resistant Pathogens for the Treatment ofSalmonellaGastroenteritis

Kalanchoe brasiliensisCambess., a Promising Natural Source of Antioxidant and Antibiotic Agents against Multidrug-Resistant Pathogens for the Treatment ofSalmonellaGastroenteritis

Natural Products as a Source for Novel Antibiotics

Chemoenzymatic Total Syntheses of Artonin I with an Intermolecular Diels–Alderase

Contact Info

Product

Resources

About