Bacterial Pyruvate Kinase: A New Potential Target to Combat Drug‐Resistant <i>Staphylococcus aureus</i> Infections

Akunuri, Ravikumar; Unnissa, Tanveer; Vadakattu, Manasa; Bujji, Sushmitha; Ghouse, Shaik Mahammad; Yaddanapudi, Venkata Madhavi; Chopra, Sidharth; Nanduri, Srinivas

doi:10.1002/slct.202201403

Cited by 4 publications

(5 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PK is an essential enzyme found in staphylococci that controls the bacteria’s growth, antibiotic resistance, and ability to create biofilms . Moreover, it was discovered to differ structurally from human homologues, making it a potential target for new antimicrobial drugs .…”

Section: Resultsmentioning

confidence: 99%

“…PK is an essential enzyme found in staphylococci that controls the bacteria’s growth, antibiotic resistance, and ability to create biofilms. 50 Moreover, it was discovered to differ structurally from human homologues, making it a potential target for new antimicrobial drugs. 51 Binding affinity and interactions with different amino acids are presented in Table 6 , and the 2D and 3D binding interactions are presented as Supporting Information .…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Antibacterial and Cytotoxicity of Extracts and Isolated Compounds from Artemisia abyssinica: A Combined Experimental and Computational Study

Tesfaye,

Endale,

Ramachandran

et al. 2024

ACS Omega

View full text Add to dashboard Cite

Artemisia abyssinica is a widely cultivated hedge plant in Ethiopia. Traditionally, they have been used to treat a variety of health conditions, including intestinal problems, infectious diseases, tonsillitis, and leishmaniasis. Silica gel chromatographic separation of the methanol and ethyl acetate extracts of the leaves, roots, and stem barks of A. abyssinica led to the isolation of 12 compounds, labeled as 1−12. Among these, compounds 1, 3, 4, 5, and 7−11 are reported as new to the genus Artemisia. The extracts and isolated compounds from A. abyssinica were evaluated for their in vitro antibacterial activity against four bacterial strains: Streptococcus pyogenes, Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, using the disc diffusion assay. All of the extracts displayed weak antibacterial activity, with inhibition zone diameters (IZDs) ranging from 6.10 ± 0.3 to 9.30 ± 0.20 mm. The isolated compounds, on the other hand, exhibited weak to moderate antibacterial activity, with IZDs ranging from 6.00 ± 0.300 to 13.50 ± 0.50 mm. The most potent antibacterial activity was observed for compound 6, which showed an IZD of 13.30 ± 0.50 mm against E. coli and 13.50 ± 0.50 mm against P. aeruginosa. This activity was comparable to that of the positive control ceftriaxone, which had IZDs of 14.1 ± 0.3 and 13.8 ± 0.5 mm against E. coli and P. aeruginosa, respectively. The in silico molecular docking analysis against DNA gyrase B revealed that compound 5 showed a higher binding affinity (−6.9 kcal/mol), followed by compound 10 (−6.7 kcal/mol) and compound 12 (−6.3 kcal/mol), whereas ciprofloxacin showed −7.3 kcal/mol. The binding affinities of compounds 5, 11, 10, and 9 were found to be −5.0, −4.3, −4.2, and −4.0 kcal/mol against S. aureus Pyruvate kinase, respectively, whereas ciprofloxacin showed a binding affinity of −4.9 kcal/mol, suggesting that compound 5 had a better binding affinity compared with ciprofloxacin. The effect of extracts of A. abyssinica was evaluated for cytotoxic activity against the breast cancer cell line (MCF-7) by the MTT assay. The extracts induced a decrease in cell viability and exerted a cytotoxic effect at a concentration of 20 μg/mL. The highest percent cell viability was observed for the methanol extract of the stem (92.9%), whereas the least was observed for the methanol extract of the root (34.5%). The result of the latter was significant compared with the positive control. The binding affinities of the isolated compounds were also assessed against human topoisomerase inhibitors IIβ. Results showed that compound 5 showed a binding affinity of −6.0 kcal/mol, followed by 11 (−5.4 kcal/mol), 10 (−5.0 kcal/mol), and 11 (−4.9 kcal/mol). Similar to ciprofloxacin, compounds 4, 5, 6, 9, 10, and 12 comply with Lipinski's rule of five. Overall, the comprehensive investigation of the chemical constituents and their biological activities reinforces the traditional medicinal applications of A. abyssinica and warrants further exploration of this plant as a source of novel therapeut...

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Antibacterial and Cytotoxicity of Extracts and Isolated Compounds from Artemisia abyssinica: A Combined Experimental and Computational Study

Tesfaye,

Endale,

Ramachandran

et al. 2024

ACS Omega

View full text Add to dashboard Cite

show abstract

“…Pyruvate kinase (PK) has been identified as a crucial enzyme in staphylococci and regulates their growth, antibiotic resistance, and biofilm formation . It was also found to be structurally distinct from human homologues, and hence, it provides a promising target for novel antimicrobial agents . For the docking studies, S.…”

Section: Resultsmentioning

confidence: 99%

“…46 It was also found to be structurally distinct from human homologues, and hence, it provides a promising target for novel antimicrobial agents. 47 For the docking studies, S. aureus PK (PDB ID: 3T07) was used as a target and ciprofloxacin was used as a reference control. Binding affinity and interactions with different amino acids are presented in Table 7.…”

Section: Boiled-egg Modelmentioning

confidence: 99%

In Silico Molecular Docking Analysis, Cytotoxicity, and Antibacterial Activities of Constituents of Fruits of Cucumis dipsaceus

Assefa,

Tesso,

Ramachandran

et al. 2023

ACS Omega

View full text Add to dashboard Cite

Cucumis dipsaceus (Cucurbitaceae) is a plant traditionally used against diarrhea, teeth-ach, wounds, stomach ache, meningitis, and cancer. The extracts of C. dipsaceus after silica gel column chromatography gave nine compounds identified using spectroscopic methods such as hexacosane (1), octadecane (2), 17-(-5-ethyl-2,6-dihydroxy-6-methylhept-3-en-2-yl)-9-(hydroxymethyl)-13-methylcyclopenta[α]phenanthren-3-ol (3), erythrodiol (4), (9,12)-propyl icosa-9,12-dienoate (5), α-spinasterol (6), 16-dehydroxycucurbitacin (7), cucurbitacin D (8), and 23,24-dihydroisocucurbitacin D (9). Compounds 3 and 4 are new to the genus Cucumis. α-Spinasterol showed better inhibition zone diameter = 13.67 ± 0.57, 15.00 ± 0.10, and 13.33 ± 0.57 mm against Escherichia coli, Pseudomonas aeruginosa, and Streptococcus pyogenes compared with the other tested samples. α-Spinasterol (−8.0 kcal/mol) and 3 (−7.6 kcal/mol) displayed high binding affinity against DNA Gyrase compared to ciprofloxacin (−7.3 kcal/mol). α-Spinasterol and 16-dehydroxycucurbitacin showed better binding affinity against protein kinase. The cytotoxicity results revealed that the EtOAc extract showed the highest potency with IC50 = 16.05 μg/mL. 16-Dehydroxycucurbitacin showed a higher binding affinity (−7.7 kcal/mol) against human topoisomerase IIβ than etoposide. The cytotoxicity and antibacterial activities and in silico molecular docking analysis displayed by the constituents corroborate the traditional use of the plant against bacteria and cancer.

show abstract

“…41 Additionally, it was discovered to be structurally unique from human homologs, making it a suitable target for new antibacterial substances. 42 For the docking studies, S. aureus PK (PDB ID: 3T07) was used as a target, and ciprofloxacin was used as a reference drug. Binding affinity and interactions with different amino acids are presented in Table 5, and the 3D and 2D binding interactions are depicted in Fig.…”

Section: Antioxidant Activitymentioning

confidence: 99%

Synthesis, dyeing performance and evaluation of the antimicrobial and antioxidant activities of azo dye derivatives incorporated with 1,3,4-thiadiazole combined within silicocomputational studies

Mezgebe,

Melaku,

Ramachandran

et al. 2024

New J. Chem.

View full text Add to dashboard Cite

show abstract

Bacterial Pyruvate Kinase: A New Potential Target to Combat Drug‐Resistant Staphylococcus aureus Infections

Abstract: insights about indole alkaloids from natural products and synthetic SAPK inhibitors along with their inhibitory properties against S. aureus and MRSA strains. This review also describes essential structural features and Structure-Activity Relationship (SAR) for SAPK inhibition.

Cited by 4 publications

References 83 publications

Antibacterial and Cytotoxicity of Extracts and Isolated Compounds from Artemisia abyssinica: A Combined Experimental and Computational Study

Antibacterial and Cytotoxicity of Extracts and Isolated Compounds from Artemisia abyssinica: A Combined Experimental and Computational Study

In Silico Molecular Docking Analysis, Cytotoxicity, and Antibacterial Activities of Constituents of Fruits of Cucumis dipsaceus

Synthesis, dyeing performance and evaluation of the antimicrobial and antioxidant activities of azo dye derivatives incorporated with 1,3,4-thiadiazole combined within silicocomputational studies

Contact Info

Product

Resources

About