Computational exploration of Picrasma quassioides compounds as CviR-mediated quorum sensing inhibitors against Chromobacterium violaceum

Bibliographic Details
Title: Computational exploration of Picrasma quassioides compounds as CviR-mediated quorum sensing inhibitors against Chromobacterium violaceum
Authors: Prasanna D. Revanasiddappa, Gowtham H. G., Chandana K. P., Shilpa Natarajamurthy, Nataraj K., Sushma Pradeep, Chandan Shivamallu, Gehan M. Elossaily, Raghu Ram Achar, Ekaterina Silina, Victor Stupin, Natalia Manturova, Ali A. Shati, Mohammad Y. Alfaifi, Serag Eldin I. Elbehairi, Amruthesh Kestur Nagaraj, Murali Mahadevamurthy, Shiva Prasad Kollur
Source: Frontiers in Chemistry, Vol 12 (2024)
Publisher Information: Frontiers Media S.A., 2024.
Publication Year: 2024
Collection: LCC:Chemistry
Subject Terms: Chromobacterium violaceum, CviR protein, in silico, Picrasma quassioides, quorum sensing, Chemistry, QD1-999
More Details: Chromobacterium violaceum an opportunistic human pathogenic bacterium, exhibits resistance to conventional antibiotics by exploiting its quorum sensing mechanism to regulate virulence factor expression. In light of this, disrupting the quorum sensing mechanism presents a promising avenue for treating infections caused by this pathogen. The study focused on using the cytoplasmic quorum sensing receptor CviR from C. violaceum as a model target to identify novel quorum sensing inhibitors from P. quassioides through in silico computational approaches. Molecular docking analyses unveiled that several phytochemicals derived from Picrasma quassioides exhibit the potential to inhibit quorum sensing by binding to CviR protein. Notably, the compounds such as Quassidine I (– 8.8 kcal/mol), Quassidine J (– 8.8 kcal/mol), Kumudine B (– 9.1 kcal/mol) and Picrasamide A (– 8.9 kcal/mol) exhibited high docking scores, indicating strong binding affinity to the CviR protein. The native ligand C6-HSL (N-hexanoyl-L-homoserine lactone) as a positive control/co-crystal inhibitor also demonstrated a significant binding energy of—7.7 kcal/mol. The molecular dynamics simulation for 200 ns showed the thermodynamic stability and binding affinity refinement of the top-ranked CviR inhibitor (Kumudine B) with its stable binding and minor fluctuations compared to positive control (C6-HSL). Pharmacokinetic predictions indicated that Kumudine B possesses favourable drug-like properties, which suggest its potential as a drug candidate. The study highlight Kumudine B as a potential agent for inhibiting the CviR protein in C. violaceum. The comprehensive evaluation of Kumudine B provides valuable insights into its pharmacological profiles, facilitating its assessment for diverse therapeutic applications and guiding future research activities, particularly as antibacterial agents for clinical drug development.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2296-2646
Relation: https://www.frontiersin.org/articles/10.3389/fchem.2024.1286675/full; https://doaj.org/toc/2296-2646
DOI: 10.3389/fchem.2024.1286675
Access URL: https://doaj.org/article/de7e4d4a139641fc86ce4d54d10c6fc0
Accession Number: edsdoj.7e4d4a139641fc86ce4d54d10c6fc0
Database: Directory of Open Access Journals
More Details
ISSN:22962646
DOI:10.3389/fchem.2024.1286675
Published in:Frontiers in Chemistry
Language:English