Synergistic antifungal activity of berberine derivative B-7b and fluconazole.
Our previous study demonstrated berberine (BBR) and fluconazole (FLC) used concomitantly exhibited a synergism against FLC-resistant Candida albicans in vitro. We also suggested BBR played a major antifungal role in the synergism of FLC and BBR, while FLC increased intracellular BBR concentrations....
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4438075?pdf=render |
| _version_ | 1828832745456926720 |
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| author | Li Ping Li Wei Liu Hong Liu Fang Zhu Da Zhi Zhang Hui Shen Zheng Xu Yun Peng Qi Shi Qun Zhang Si Min Chen Li Juan He Xin Ju Cao Xin Huang Jun Dong Zhang Lan Yan Mao Mao An Yuan Ying Jiang |
| author_facet | Li Ping Li Wei Liu Hong Liu Fang Zhu Da Zhi Zhang Hui Shen Zheng Xu Yun Peng Qi Shi Qun Zhang Si Min Chen Li Juan He Xin Ju Cao Xin Huang Jun Dong Zhang Lan Yan Mao Mao An Yuan Ying Jiang |
| author_sort | Li Ping Li |
| collection | DOAJ |
| description | Our previous study demonstrated berberine (BBR) and fluconazole (FLC) used concomitantly exhibited a synergism against FLC-resistant Candida albicans in vitro. We also suggested BBR played a major antifungal role in the synergism of FLC and BBR, while FLC increased intracellular BBR concentrations. Our following systematic structural modification and reconstruction of BBR core identified the novel scaffold of N-(2-(benzo[d][1,3]dioxol-5-yl)ethyl)-2-(substituted phenyl)acet-amide derivatives 7a-i, including B-7b and B-7d exhibiting remarkable synergistic antifungal activity and low cytotoxicity. Here, the study mainly investigated the synergistic activity of FLC and B-7b and the underlying mechanism. In vitro interaction of FLC and B-7b was investigated against 30 FLC-resistant clinical isolates of C. albicans and non-C. albicans species, including Candida tropicalis, Candida parapsilosis, Candida glabrata, Candida krusei and Cryptococcus neoformans. The potent synergistic activity of B-7b in combination with FLC against FLC-resistant C. albicans was found through the checkerboard microdilution assay. The findings of agar diffusion tests and time-kill curves confirmed its better synergism with FLC. And as expected, B-7b exhibited much lower cytotoxicity than BBR to human umbilical vein endothelial cells. In contrast to BBR, we found that endogenous ROS augmentation was not involved in the synergism of FLC and B-7b. According to the results from our present comparative proteomic study, it seemed that the disruption of protein folding and processing and the weakening of cells' self-defensive ability contributed to the synergism of FLC and B-7b. Together, these results suggested novel scaffold BBR derivative B-7b could be a promising synergist in combination with FLC for the treatment of invasive fungal infections. |
| first_indexed | 2024-12-12T17:00:31Z |
| format | Article |
| id | doaj.art-8d58d315ced842f3befa5ef73a1853e6 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T17:00:31Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj.art-8d58d315ced842f3befa5ef73a1853e62022-12-22T00:18:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01105e012639310.1371/journal.pone.0126393Synergistic antifungal activity of berberine derivative B-7b and fluconazole.Li Ping LiWei LiuHong LiuFang ZhuDa Zhi ZhangHui ShenZheng XuYun Peng QiShi Qun ZhangSi Min ChenLi Juan HeXin Ju CaoXin HuangJun Dong ZhangLan YanMao Mao AnYuan Ying JiangOur previous study demonstrated berberine (BBR) and fluconazole (FLC) used concomitantly exhibited a synergism against FLC-resistant Candida albicans in vitro. We also suggested BBR played a major antifungal role in the synergism of FLC and BBR, while FLC increased intracellular BBR concentrations. Our following systematic structural modification and reconstruction of BBR core identified the novel scaffold of N-(2-(benzo[d][1,3]dioxol-5-yl)ethyl)-2-(substituted phenyl)acet-amide derivatives 7a-i, including B-7b and B-7d exhibiting remarkable synergistic antifungal activity and low cytotoxicity. Here, the study mainly investigated the synergistic activity of FLC and B-7b and the underlying mechanism. In vitro interaction of FLC and B-7b was investigated against 30 FLC-resistant clinical isolates of C. albicans and non-C. albicans species, including Candida tropicalis, Candida parapsilosis, Candida glabrata, Candida krusei and Cryptococcus neoformans. The potent synergistic activity of B-7b in combination with FLC against FLC-resistant C. albicans was found through the checkerboard microdilution assay. The findings of agar diffusion tests and time-kill curves confirmed its better synergism with FLC. And as expected, B-7b exhibited much lower cytotoxicity than BBR to human umbilical vein endothelial cells. In contrast to BBR, we found that endogenous ROS augmentation was not involved in the synergism of FLC and B-7b. According to the results from our present comparative proteomic study, it seemed that the disruption of protein folding and processing and the weakening of cells' self-defensive ability contributed to the synergism of FLC and B-7b. Together, these results suggested novel scaffold BBR derivative B-7b could be a promising synergist in combination with FLC for the treatment of invasive fungal infections.http://europepmc.org/articles/PMC4438075?pdf=render |
| spellingShingle | Li Ping Li Wei Liu Hong Liu Fang Zhu Da Zhi Zhang Hui Shen Zheng Xu Yun Peng Qi Shi Qun Zhang Si Min Chen Li Juan He Xin Ju Cao Xin Huang Jun Dong Zhang Lan Yan Mao Mao An Yuan Ying Jiang Synergistic antifungal activity of berberine derivative B-7b and fluconazole. PLoS ONE |
| title | Synergistic antifungal activity of berberine derivative B-7b and fluconazole. |
| title_full | Synergistic antifungal activity of berberine derivative B-7b and fluconazole. |
| title_fullStr | Synergistic antifungal activity of berberine derivative B-7b and fluconazole. |
| title_full_unstemmed | Synergistic antifungal activity of berberine derivative B-7b and fluconazole. |
| title_short | Synergistic antifungal activity of berberine derivative B-7b and fluconazole. |
| title_sort | synergistic antifungal activity of berberine derivative b 7b and fluconazole |
| url | http://europepmc.org/articles/PMC4438075?pdf=render |
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