Bioactivity of melianone against Salmonella and in silico prediction of a membrane protein target

Veni, Amalanathan; Lokeswari, T. S.; Kumari, G. N. Krishna; Gayathri, D.; Sudandiradoss, C.

doi:10.1007/s13205-020-02441-9

Cited by 2 publications

(1 citation statement)

References 37 publications

(41 reference statements)

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“…Moreover, C3 (Zhao et al, 2019) was active against Salmonella ser. typhi with both MIC and MBC of 0.053 µM (Veni et al, 2020) against S. aureus with agar diffusion inhibition zone of 9 mm (Biavatti et al, 2001), and it was also documented for anticancer, antivirus, anti-gout, anti-depressant, and antifeeding activities (Su et al, 1990;Ishaq, 2016;Liu Y. et al, 2019;Zhao et al, 2019;Anita and Praveena, 2020;Sundar and Aarthy, 2020).…”

Section: Bioactivity Discussion Of Kumu Compoundsmentioning

confidence: 92%

Bioassay-Guided Interpretation of Antimicrobial Compounds in Kumu, a TCM Preparation From Picrasma quassioides’ Stem via UHPLC-Orbitrap-Ion Trap Mass Spectrometry Combined With Fragmentation and Retention Time Calculation

Peng

et al. 2021

Front. Pharmacol.

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The stem of Picrasma quassioides (PQ) was recorded as a prominent traditional Chinese medicine, Kumu, which was effective for microbial infection, inflammation, fever, and dysentery, etc. At present, Kumu is widely used in China to develop different medicines, even as injection (Kumu zhusheye), for combating infections. However, the chemical basis of its antimicrobial activity has still not been elucidated. To examine the active chemicals, its stem was extracted to perform bioassay-guided purification against Staphylococcus aureus and Escherichia coli. In this study, two types of columns (normal and reverse-phase) were used for speedy bioassay-guided isolation from Kumu, and the active peaks were collected and identified via an UHPLC-Orbitrap-Ion Trap Mass Spectrometer, combined with MS Fragmenter and ChromGenius. For identification, the COCONUT Database (largest database of natural products) and a manually built PQ database were used, in combination with prediction and calculation of mass fragmentation and retention time to better infer their structures, especially for isomers. Moreover, three standards were analyzed under different conditions for developing and validating the MS method. A total of 25 active compounds were identified, including 24 alkaloids and 1 triterpenoid against S. aureus, whereas only β-carboline-1-carboxylic acid and picrasidine S were active against E. coli. Here, the good antimicrobial activity of 18 chemicals was reported for the first time. Furthermore, the spectrum of three abundant β-carbolines was assessed via their IC50 and MBC against various human pathogens. All of them exhibited strong antimicrobial activities with good potential to be developed as antibiotics. This study clearly showed the antimicrobial chemical basis of Kumu, and the results demonstrated that HRMS coupled with MS Fragmenter and ChromGenius was a powerful tool for compound analysis, which can be used for other complex samples. Beta-carbolines reported here are important lead compounds in antibiotic discovery.

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Section: Bioactivity Discussion Of Kumu Compoundsmentioning

confidence: 92%

Bioassay-Guided Interpretation of Antimicrobial Compounds in Kumu, a TCM Preparation From Picrasma quassioides’ Stem via UHPLC-Orbitrap-Ion Trap Mass Spectrometry Combined With Fragmentation and Retention Time Calculation

Peng

et al. 2021

Front. Pharmacol.

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Melianone inhibits Secreted Aspartic Proteases (SAP), a Virulence Factor During Hyphal Formation in Candida albicans

Veni

Lokeswari

Pavithra

et al. 2022

CAD

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Background & Objective: Candida albicans (C.-P. Robin) Berkhout, the pathogenic yeasts’ ability to transform from yeast to hyphal forms in the bloodstream is essential during systemic infections. Among the several virulence factors studied, secreted aspartic proteinases (SAPs) involved in hyphal penetration are targets of putative hyphal inhibitors. Upregulation of SAP6 gene, (two-to 31- fold high) during budded to hyphal transition and lack of studies on its inhibition, prompted us to investigate this particular protein using in silico tools. Results: Hyphal inhibition of germinating yeast cells by melianone, a triterpenoid, from Swietenia mahagoni (L.) Jacq. (Meliaceae) was observed at 0.1 µM (IC50). One of the targets of putative hyphal inhibitors, SAP, was assayed and for the first time, 50 % of the biological SAP activity was found to be inhibited by melianone at 0.125 µM. This data on SAP inhibition led us to analyse the 3-dimensional structure for SAP6 protein that was constructed through a combination of homology modelling and ab-initio method (Phyre2) and validated before performing Induced Fit Docking (IFD). Melianone formed H-bond and hydrophobic interactions with the crucial residues (ASP108, TYR160, ALA161, ASP162, ASP294, THR297, ASP379) in the catalytic site of SAP6 with a glide energy (-)54.9327 kcal mol-1 upon Induced Fit Docking (IFD). Conclusion: We report here for the first time on the SAP inhibitory ability of melianone at 0.125 uM. Being a small molecular mass inhibitor, binding with high affinity to the S3 pocket sites of SAP proteins provide evidence for pre-clinical testing of such compounds against fungal pathogens.

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Bioactivity of melianone against Salmonella and in silico prediction of a membrane protein target

Cited by 2 publications

References 37 publications

Bioassay-Guided Interpretation of Antimicrobial Compounds in Kumu, a TCM Preparation From Picrasma quassioides’ Stem via UHPLC-Orbitrap-Ion Trap Mass Spectrometry Combined With Fragmentation and Retention Time Calculation

Bioassay-Guided Interpretation of Antimicrobial Compounds in Kumu, a TCM Preparation From Picrasma quassioides’ Stem via UHPLC-Orbitrap-Ion Trap Mass Spectrometry Combined With Fragmentation and Retention Time Calculation

Melianone inhibits Secreted Aspartic Proteases (SAP), a Virulence Factor During Hyphal Formation in Candida albicans

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