Dithiocarbamate fungicides suppress aromatase activity in human and rat aromatase activity depending on structures: 3D-QSAR analysis and molecular simulation

doi:10.1080/1062936X.2024.2420243

科研成果详情

题名	Dithiocarbamate fungicides suppress aromatase activity in human and rat aromatase activity depending on structures: 3D-QSAR analysis and molecular simulation
作者	Ji, Z.1,2,3,4,5; Chen, H.6; Zheng, J. I.2,3,4,5; Yan, J.3,4,5; Lu, H.1,2; He, J.2,3,4,5; Zhu, Y.1,2,3,4,5,7,8; Wang, S.1,2; Li, L.1,2; Ge, R. S.1,2,3,4,5,6,7,8; Liu, Y.1,2
发表日期	2024-11-01
发表期刊	SAR AND QSAR IN ENVIRONMENTAL RESEARCH 影响因子和分区
语种	英语
原始文献类型	Article ; Early Access
关键词	Dithiocarbamates zineb oestradiol log P docking
其他关键词	ZIRAM ; EXPOSURE ; PESTICIDES
摘要	Dithiocarbamate fungicides have been widely used in agricultural practices due to their effective control of fungal diseases, thereby contributing to global food security and agricultural productivity. In this study, the inhibitory potency of eight compounds on human and rat aromatase (CYP19A1) activity was evaluated. The results revealed that zineb exhibited the highest inhibitory potency on human CYP19A1 (IC50, 2.79 mu M). Maneb (IC50, 3.09 mu M), thiram (IC50, 4.76 mu M), and ferbam (IC50, 6.04 mu M) also demonstrated potent inhibition on human CYP19A1. For the rat CYP19A1, disulfiram (IC50, 1.90 mu M) displayed the strongest inhibition followed by maneb (2.16 mu M), zineb (2.54 mu M), and thiram (6.99 mu M). These dithiocarbamates acted as mixed/non-competitive inhibitors of human and rat CYP19A1. Dithiothreitol (DTT), a reducing agent, partially rescued thiram-mediated inhibition when incubated at the same. Moreover, positive correlations were observed between log P, topological polar surface area, molecular weight, and heavy atoms and IC50 values. 3D-QSAR analysis revealed the hydrogen bond acceptor and donor play critical roles in the binding of dithiocarbamates to human CYP19A1. In silico analysis showed that dithiocarbamates bind to the haem binding site, containing Cys437 residues. In conclusion, some dithiocarbamates potently inhibit human and rat CYP19A1 via interacting with haem-binding Cys437 residues.
资助项目	Zhejiang Nature Science; Scientific Research Center of Wenzhou Medical University
出版者	TAYLOR & FRANCIS LTD
ISSN	1062-936X
EISSN	1029-046X
卷号	35 期号:10 页码:949-970
DOI	10.1080/1062936X.2024.2420243
页数	22
WOS类目	Chemistry, Multidisciplinary ; Computer Science, Interdisciplinary Applications ; Environmental Sciences ; Mathematical & Computational Biology ; Toxicology
WOS研究方向	Chemistry ; Computer Science ; Environmental Sciences & Ecology ; Mathematical & Computational Biology ; Toxicology
WOS记录号	WOS:001347023100001
收录类别	SCIE ; PUBMED ; EI
EI入藏号	20244717388453
EI主题词	Hydrogen bonds
EI分类号	103 ; 801.1 Chemistry, General ; 801.3 Colloid Chemistry ; 803 Chemical Agents and Basic Industrial Chemicals ; 821 Agricultural Equipment and Methods ; Vegetation and Pest Control
URL	查看原文
PubMed ID	39475673
通讯作者地址	[Li, L.;Ge, R. S.;Liu, Y.]Wenzhou Med Univ, Affiliated Hosp 2, Dept Gynecol & Obstet, Wenzhou, Zhejiang, Peoples R China. ; [Li, L.;Ge, R. S.;Liu, Y.]Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou, Zhejiang, Peoples R China. ; [Ge, R. S.]Second Affiliated Hosp, Dept Anesthesiol & Perioperat Med, Wenzhou, Zhejiang, Peoples R China. ; [Ge, R. S.]Minist Educ, Key Lab Pediat Anesthesiol, Wenzhou, Zhejiang, Peoples R China. ; [Ge, R. S.]Wenzhou Med Univ, Key Lab Anesthesiol Zhejiang Prov, Wenzhou, Zhejiang, Peoples R China. ; [Ge, R. S.]Wenzhou Med Univ, Dingli Clin Coll, Dept Emergency, Wenzhou, Zhejiang, Peoples R China. ; [Ge, R. S.]Wenzhou Med Univ, Affiliated Hosp 2, Key Lab Environm & Male Reprod Med Wenzhou, Wenzhou, Zhejiang, Peoples R China. ; [Ge, R. S.]Wenzhou Med Univ, Yuying Childrens Hosp, Key Lab Struct Malformat Children Zhejiang Prov, Wenzhou, Zhejiang, Peoples R China.
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/221353
专题	附属第二医院_妇产科附属第二医院第二临床医学院，附属第二医院、育英儿童医院附属第二医院_麻醉重点学科实验室其他_定理临床学院（温州市中心医院）
通讯作者	Li, L.; Ge, R. S.; Liu, Y.
作者单位	1.Wenzhou Med Univ, Affiliated Hosp 2, Dept Gynecol & Obstet, Wenzhou, Zhejiang, Peoples R China; 2.Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou, Zhejiang, Peoples R China; 3.Second Affiliated Hosp, Dept Anesthesiol & Perioperat Med, Wenzhou, Zhejiang, Peoples R China; 4.Minist Educ, Key Lab Pediat Anesthesiol, Wenzhou, Zhejiang, Peoples R China; 5.Wenzhou Med Univ, Key Lab Anesthesiol Zhejiang Prov, Wenzhou, Zhejiang, Peoples R China; 6.Wenzhou Med Univ, Dingli Clin Coll, Dept Emergency, Wenzhou, Zhejiang, Peoples R China; 7.Wenzhou Med Univ, Affiliated Hosp 2, Key Lab Environm & Male Reprod Med Wenzhou, Wenzhou, Zhejiang, Peoples R China; 8.Wenzhou Med Univ, Yuying Childrens Hosp, Key Lab Struct Malformat Children Zhejiang Prov, Wenzhou, Zhejiang, Peoples R China
第一作者单位	附属第二医院_妇产科; 第二临床医学院，附属第二医院、育英儿童医院; 附属第二医院_麻醉重点学科实验室
通讯作者单位	附属第二医院_妇产科; 第二临床医学院，附属第二医院、育英儿童医院; 附属第二医院_麻醉重点学科实验室; 其他_定理临床学院（温州市中心医院）; 附属第二医院
第一作者的第一单位	附属第二医院_妇产科
推荐引用方式 GB/T 7714	Ji, Z.,Chen, H.,Zheng, J. I.,et al. Dithiocarbamate fungicides suppress aromatase activity in human and rat aromatase activity depending on structures: 3D-QSAR analysis and molecular simulation[J]. SAR AND QSAR IN ENVIRONMENTAL RESEARCH,2024,35(10):949-970.
APA	Ji, Z.., Chen, H.., Zheng, J. I.., Yan, J.., Lu, H.., ... & Liu, Y.. (2024). Dithiocarbamate fungicides suppress aromatase activity in human and rat aromatase activity depending on structures: 3D-QSAR analysis and molecular simulation. SAR AND QSAR IN ENVIRONMENTAL RESEARCH, 35(10), 949-970.
MLA	Ji, Z.,et al."Dithiocarbamate fungicides suppress aromatase activity in human and rat aromatase activity depending on structures: 3D-QSAR analysis and molecular simulation".SAR AND QSAR IN ENVIRONMENTAL RESEARCH 35.10(2024):949-970.