Chengjie Ji1, Guang Xin2, Feixia Duan3, Wen Huang2, Taichang Tan1. 1. Department of Laboratory Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 611731, China. 2. Laboratory of Ethnopharmacology, Regenerative Medicine Research Center, Institute for Nanobiomedical Technology and Membrane Biology, West China Hospital/West China Medical School, Sichuan University, Chengdu 610041, China. 3. College of Light Industry, Textile and Food Engineering, Sichuan University, Chengdu, Sichuan 610065, China.
Abstract
BACKGROUND: Novel haloemodin (HEI2) synthesized by modifying emodin, a traditional Chinese medicine component, possesses remarkable antibacterial activity, being much more effective than its parent nucleus, emodin. METHODS: Firstly, we discovered that HEI2 increases bacterial cell membrane permeability to potassium ions more drastically than emodin. We thus further investigated the interaction of haloemodin and protein using a fluorescence quenching and circular dichroism (CD) study based on bovine serum albumin (BSA). RESULTS: HEI2 spontaneously bound to BSA at Trp 212 residue (subdomain IIA) by hydrogen bonds and van der Waals interactions to forms HEI2-BSA complexes, and this binding decreased the α-helical content of BSA. We also confirmed that emodin bound to BSA by hydrophobic interaction alone. CONCLUSIONS: These results suggest that the main responses for the substantial antibacterial activities of HEI2 are a disruption of the bacterial plasma membrane function and the interaction with biological functional proteins. Furthermore, the study of the interaction of drugs with BSA, which has a fluorescent group tryptophan residue similar to many bio-functional proteins, will be a simple and inexpensive scope-reducing method in screening new drugs. 2020 Annals of Translational Medicine. All rights reserved.
BACKGROUND: Novel haloemodin (HEI2) synthesized by modifying emodin, a traditional Chinese medicine component, possesses remarkable antibacterial activity, being much more effective than its parent nucleus, emodin. METHODS: Firstly, we discovered that HEI2 increases bacterial cell membrane permeability to potassium ions more drastically than emodin. We thus further investigated the interaction of haloemodin and protein using a fluorescence quenching and circular dichroism (CD) study based on bovine serum albumin (BSA). RESULTS: HEI2 spontaneously bound to BSA at Trp 212 residue (subdomain IIA) by hydrogen bonds and van der Waals interactions to forms HEI2-BSA complexes, and this binding decreased the α-helical content of BSA. We also confirmed that emodin bound to BSA by hydrophobic interaction alone. CONCLUSIONS: These results suggest that the main responses for the substantial antibacterial activities of HEI2 are a disruption of the bacterial plasma membrane function and the interaction with biological functional proteins. Furthermore, the study of the interaction of drugs with BSA, which has a fluorescent group tryptophan residue similar to many bio-functional proteins, will be a simple and inexpensive scope-reducing method in screening new drugs. 2020 Annals of Translational Medicine. All rights reserved.