Olusola Bodede1, Shakira Shaik2, Hafizah Chenia2, Parvesh Singh1, Roshila Moodley3. 1. School of Chemistry and Physics, University of KwaZulu-Natal, Westville Campus, Private Bag X54001, Durban 4000, South Africa. 2. School of Life Sciences, University of KwaZulu-Natal, Westville Campus, Private Bag X54001, Durban 4000, South Africa. 3. School of Chemistry and Physics, University of KwaZulu-Natal, Westville Campus, Private Bag X54001, Durban 4000, South Africa. Electronic address: moodleyrosh@ukzn.ac.za.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Senegalia nigrescens is used in traditional medicine for the treatment of dysentery and convulsions. AIMS OF THE STUDY: This study was aimed at identifying bioactive compounds from S. nigrescens and carrying out in vitro and in silico anti-quorum sensing studies on the compounds. MATERIALS AND METHODS: Extracts of S. nigrescens were chromatographed repeatedly. The isolated compounds were characterised using NMR spectroscopy and mass spectrometry. The anti-quorum sensing potential of S. nigrescens crude extracts and selected phytochemicals was quantified using Chromobacterium violaceum quorum sensing-controlled violacein inhibition assays. Qualitative modulation of quorum sensing activity and signal synthesis was investigated using agar diffusion double ring assays and C. violaceum. Molecular docking was conducted to explore the binding conformations of ent-kaurene diterpenes and flavonoids into the binding sites of quorum sensing regulator proteins, CviR and CviR'. RESULTS: Phytochemical investigation of S. nigrescens resulted in the isolation of a new ent-kaurene diterpenoid (ent-kaur-15-en-18,20-diol) alongside ent-kaur-15-en-18-ol, being isolated for the first time from a plant species. Other compounds isolated included 30-hydroxylup-20(29)-en-3β-ol, 3β-hydroxy-20(29)-en-lupan-30-al, lupeol, stigmasterol, a long chain alcohol (tetracosan-1-ol) and three flavonoids (melanoxetin, quercetin and quercetin-3-O-methyl ether). Structures of isolated compounds were elucidated using different spectroscopic techniques including 1D and 2D NMR. Inhibition of violacein production was concentration-dependent, with 56.52% inhibition being obtained with 200 µg of quercetin-3-O-methyl ether, while 53.38% inhibition was obtained with 600 µg of quercetin. Agar diffusion double ring assays indicated CviI synthase/CviR receptor modulation by S. nigrescens phytochemicals, suggesting that quorum signal synthesis was down-regulated and/or targeting binding of signal to the receptor. The computed binding energy data suggested that the flavonoids had a stronger tendency to inhibit both CviR and CviR' with varying binding affinities. CONCLUSION: S. nigrescens crude extracts together with the novel ent-kaurenoids and flavonoids demonstrated potential anti-quorum sensing activity. S. nigrescens may thus represent a source of anti-quorum sensing therapeutic candidates for the control of existing and emerging infectious diseases.
ETHNOPHARMACOLOGICAL RELEVANCE: Senegalia nigrescens is used in traditional medicine for the treatment of dysentery and convulsions. AIMS OF THE STUDY: This study was aimed at identifying bioactive compounds from S. nigrescens and carrying out in vitro and in silico anti-quorum sensing studies on the compounds. MATERIALS AND METHODS: Extracts of S. nigrescens were chromatographed repeatedly. The isolated compounds were characterised using NMR spectroscopy and mass spectrometry. The anti-quorum sensing potential of S. nigrescens crude extracts and selected phytochemicals was quantified using Chromobacterium violaceum quorum sensing-controlled violacein inhibition assays. Qualitative modulation of quorum sensing activity and signal synthesis was investigated using agar diffusion double ring assays and C. violaceum. Molecular docking was conducted to explore the binding conformations of ent-kaurenediterpenes and flavonoids into the binding sites of quorum sensing regulator proteins, CviR and CviR'. RESULTS: Phytochemical investigation of S. nigrescens resulted in the isolation of a new ent-kaurenediterpenoid (ent-kaur-15-en-18,20-diol) alongside ent-kaur-15-en-18-ol, being isolated for the first time from a plant species. Other compounds isolated included 30-hydroxylup-20(29)-en-3β-ol, 3β-hydroxy-20(29)-en-lupan-30-al, lupeol, stigmasterol, a long chain alcohol (tetracosan-1-ol) and three flavonoids (melanoxetin, quercetin and quercetin-3-O-methyl ether). Structures of isolated compounds were elucidated using different spectroscopic techniques including 1D and 2D NMR. Inhibition of violacein production was concentration-dependent, with 56.52% inhibition being obtained with 200 µg of quercetin-3-O-methyl ether, while 53.38% inhibition was obtained with 600 µg of quercetin. Agar diffusion double ring assays indicated CviI synthase/CviR receptor modulation by S. nigrescens phytochemicals, suggesting that quorum signal synthesis was down-regulated and/or targeting binding of signal to the receptor. The computed binding energy data suggested that the flavonoids had a stronger tendency to inhibit both CviR and CviR' with varying binding affinities. CONCLUSION:S. nigrescens crude extracts together with the novel ent-kaurenoids and flavonoids demonstrated potential anti-quorum sensing activity. S. nigrescens may thus represent a source of anti-quorum sensing therapeutic candidates for the control of existing and emerging infectious diseases.
Authors: Alexey S Vasilchenko; Darya V Poshvina; Roman Yu Sidorov; Aleksandr V Iashnikov; Eugene A Rogozhin; Anastasia V Vasilchenko Journal: World J Microbiol Biotechnol Date: 2022-08-16 Impact factor: 4.253
Authors: E Paluch; J Rewak-Soroczyńska; I Jędrusik; E Mazurkiewicz; K Jermakow Journal: Appl Microbiol Biotechnol Date: 2020-01-11 Impact factor: 4.813