Structure-activity relationship and in silico docking analysis of dicarboximide fungicides on 17β-hydroxysteroid dehydrogenase 1 of human, rat, and pig
Dicarboximide fungicides, including captafol, captan, cyclohexylthiophthalimide, folpet, and procymidone, represent a distinct category of fungicides. 17β-Hydroxysteroid dehydrogenase 1 (17β-HSD1) catalyzes the conversion of estrone to estradiol in mammals. Yet, the impact of these fungicides on 17β...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-01-01
|
| Series: | Ecotoxicology and Environmental Safety |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651324016051 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1823856891319549952 |
|---|---|
| author | Huiqian Chen Sailing Chen Yunbing Tang Yingfen Ying Shaowei Wang Yang Zhu Yiyan Wang Ren-shan Ge Ping Duan |
| author_facet | Huiqian Chen Sailing Chen Yunbing Tang Yingfen Ying Shaowei Wang Yang Zhu Yiyan Wang Ren-shan Ge Ping Duan |
| author_sort | Huiqian Chen |
| collection | DOAJ |
| description | Dicarboximide fungicides, including captafol, captan, cyclohexylthiophthalimide, folpet, and procymidone, represent a distinct category of fungicides. 17β-Hydroxysteroid dehydrogenase 1 (17β-HSD1) catalyzes the conversion of estrone to estradiol in mammals. Yet, the impact of these fungicides on 17β-HSD1 activity remains unknown. In this study, we investigated their inhibition using human placental cytosols, rat and pig ovarian cytosols. Our observations revealed that dicarboximide fungicides significantly inhibited human 17β-HSD1 activity. Among them, captan showed the strongest potency, with its IC50 of 1.28 μM, whereas procymidone had an IC50 of 100.71 μM. However, both rat and pig 17β-HSD1 enzymes were less sensitive to the inhibition of these fungicides compared to the human enzyme, with captan displaying an IC50 of 5.65 μM for the rat enzyme and 7.36 μM for the pig enzyme. Correlation analysis indicated a positive correlation between IC50 values and LogP. Docking analysis revealed that these fungicides bound to cofactor or between the steroid and cofactor binding sites. The dithiothreitol treatment demonstrated that the formation of irreversible bonds between dicarboximide fungicides and the cysteine residues played a key role in the inhibition of 17β-HSD1 activity. In conclusion, dicarboximide fungicides inhibit 17β-HSD1 depending on lipophilicity, species, and cysteine residue interactions. |
| format | Article |
| id | doaj-art-304c273b453942aca2d7b380143c2737 |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-304c273b453942aca2d7b380143c27372025-02-12T05:29:31ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01290117529Structure-activity relationship and in silico docking analysis of dicarboximide fungicides on 17β-hydroxysteroid dehydrogenase 1 of human, rat, and pigHuiqian Chen0Sailing Chen1Yunbing Tang2Yingfen Ying3Shaowei Wang4Yang Zhu5Yiyan Wang6Ren-shan Ge7Ping Duan8Department of Obstetrics and Gynecology, Oncology Discipline Group, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, ChinaDepartment of Obstetrics and Gynecology, Oncology Discipline Group, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, ChinaDepartment of Obstetrics and Gynecology, Oncology Discipline Group, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, ChinaDepartment of Obstetrics and Gynecology, Oncology Discipline Group, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, ChinaDepartment of Obstetrics and Gynecology, Oncology Discipline Group, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, ChinaDepartment of Anesthesiology and Perioperative Medicine, the Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang 325027, ChinaDepartment of Anesthesiology and Perioperative Medicine, the Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang 325027, ChinaDepartment of Obstetrics and Gynecology, Oncology Discipline Group, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China; Department of Anesthesiology and Perioperative Medicine, the Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Male Health and Environment of Wenzhou, Wenzhou Medical University, Zhejiang 325000, China; Correspondence to: Department of Obstetrics and Gynecology, Oncology Discipline Group, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.Department of Obstetrics and Gynecology, Oncology Discipline Group, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China; Correspondence to: Department of Obstetrics and Gynecology, Oncology Discipline Group, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.Dicarboximide fungicides, including captafol, captan, cyclohexylthiophthalimide, folpet, and procymidone, represent a distinct category of fungicides. 17β-Hydroxysteroid dehydrogenase 1 (17β-HSD1) catalyzes the conversion of estrone to estradiol in mammals. Yet, the impact of these fungicides on 17β-HSD1 activity remains unknown. In this study, we investigated their inhibition using human placental cytosols, rat and pig ovarian cytosols. Our observations revealed that dicarboximide fungicides significantly inhibited human 17β-HSD1 activity. Among them, captan showed the strongest potency, with its IC50 of 1.28 μM, whereas procymidone had an IC50 of 100.71 μM. However, both rat and pig 17β-HSD1 enzymes were less sensitive to the inhibition of these fungicides compared to the human enzyme, with captan displaying an IC50 of 5.65 μM for the rat enzyme and 7.36 μM for the pig enzyme. Correlation analysis indicated a positive correlation between IC50 values and LogP. Docking analysis revealed that these fungicides bound to cofactor or between the steroid and cofactor binding sites. The dithiothreitol treatment demonstrated that the formation of irreversible bonds between dicarboximide fungicides and the cysteine residues played a key role in the inhibition of 17β-HSD1 activity. In conclusion, dicarboximide fungicides inhibit 17β-HSD1 depending on lipophilicity, species, and cysteine residue interactions.http://www.sciencedirect.com/science/article/pii/S0147651324016051Dicarboximide fungicides17β-HSD1Estradiol synthesisDocking analysisCysteine |
| spellingShingle | Huiqian Chen Sailing Chen Yunbing Tang Yingfen Ying Shaowei Wang Yang Zhu Yiyan Wang Ren-shan Ge Ping Duan Structure-activity relationship and in silico docking analysis of dicarboximide fungicides on 17β-hydroxysteroid dehydrogenase 1 of human, rat, and pig Ecotoxicology and Environmental Safety Dicarboximide fungicides 17β-HSD1 Estradiol synthesis Docking analysis Cysteine |
| title | Structure-activity relationship and in silico docking analysis of dicarboximide fungicides on 17β-hydroxysteroid dehydrogenase 1 of human, rat, and pig |
| title_full | Structure-activity relationship and in silico docking analysis of dicarboximide fungicides on 17β-hydroxysteroid dehydrogenase 1 of human, rat, and pig |
| title_fullStr | Structure-activity relationship and in silico docking analysis of dicarboximide fungicides on 17β-hydroxysteroid dehydrogenase 1 of human, rat, and pig |
| title_full_unstemmed | Structure-activity relationship and in silico docking analysis of dicarboximide fungicides on 17β-hydroxysteroid dehydrogenase 1 of human, rat, and pig |
| title_short | Structure-activity relationship and in silico docking analysis of dicarboximide fungicides on 17β-hydroxysteroid dehydrogenase 1 of human, rat, and pig |
| title_sort | structure activity relationship and in silico docking analysis of dicarboximide fungicides on 17β hydroxysteroid dehydrogenase 1 of human rat and pig |
| topic | Dicarboximide fungicides 17β-HSD1 Estradiol synthesis Docking analysis Cysteine |
| url | http://www.sciencedirect.com/science/article/pii/S0147651324016051 |
| work_keys_str_mv | AT huiqianchen structureactivityrelationshipandinsilicodockinganalysisofdicarboximidefungicideson17bhydroxysteroiddehydrogenase1ofhumanratandpig AT sailingchen structureactivityrelationshipandinsilicodockinganalysisofdicarboximidefungicideson17bhydroxysteroiddehydrogenase1ofhumanratandpig AT yunbingtang structureactivityrelationshipandinsilicodockinganalysisofdicarboximidefungicideson17bhydroxysteroiddehydrogenase1ofhumanratandpig AT yingfenying structureactivityrelationshipandinsilicodockinganalysisofdicarboximidefungicideson17bhydroxysteroiddehydrogenase1ofhumanratandpig AT shaoweiwang structureactivityrelationshipandinsilicodockinganalysisofdicarboximidefungicideson17bhydroxysteroiddehydrogenase1ofhumanratandpig AT yangzhu structureactivityrelationshipandinsilicodockinganalysisofdicarboximidefungicideson17bhydroxysteroiddehydrogenase1ofhumanratandpig AT yiyanwang structureactivityrelationshipandinsilicodockinganalysisofdicarboximidefungicideson17bhydroxysteroiddehydrogenase1ofhumanratandpig AT renshange structureactivityrelationshipandinsilicodockinganalysisofdicarboximidefungicideson17bhydroxysteroiddehydrogenase1ofhumanratandpig AT pingduan structureactivityrelationshipandinsilicodockinganalysisofdicarboximidefungicideson17bhydroxysteroiddehydrogenase1ofhumanratandpig |