Iron transport mediated delivery of pyochelin-zingerone conjugate: a trojan horse strategy against pseudomonas aeruginosa
| PI Details | Co-PI Details |
|---|---|
|
Dr. Kusum Harjai
Designation: Professor |
Dr. Sanjay Chhibber
Dr. Sanjay Chhibber Dr. Vasundhara Singh |
| Funding Agency | Project Cost |
|---|---|
| Department of Science and Technology- Science Engineering Research Board |
Rs. 36,77,434 |
| Start Date | Completion Date | Status |
|---|---|---|
| 2018-12-15 | 2021-12-15 | Completed |
Abstract
The conjugate was found to be QS inhibitor. It also showed potent in vitro inhibitory activity against biofilm formation due to reduction in twitching, swimming, and swarming motilities of P. aeruginosa. In silico molecular docking studies suggested that PZC 4 binds with the FptA, the outer membrane receptor of pyochelin indicating delivery of conjugate hence zingerone, inside the target organism. PZC possess therapeutic value as a ‘Trojan Horse’ entity and conjugate is transported inside the bacterium effectively through iron transport system after binding with siderophore receptor. PZC has been shown to have hepatoprotective potential in P. aeruginosa induced peritonitis mice model Therefore, this represents an innovative approach against multi-drug resistant Gram-negative bacterium P. aeruginosa. Hence, this study opens a path to employ PZC as potential drug candidate to suppress P. aeruginosa mediated infections. It can help in overcoming resistance.
| Manpower Sanctioned/Hired | Manpower Trained |
|---|---|
|
JRF- 1 |
PhD produced- 1 |
Equipment Sanctioned/Procured
|
Name of Equipment |
Make & Model |
Year of Purchase |
Cost |
Salient features of Equipment |
Condition |
|---|---|---|---|---|---|
|
UV-Spectrophotometer |
LabIndia |
2019 |
3,67,458 |
Spectrophotometer to observe the optical density |
Working |
|
HPLC Columns |
Sunfire C-18 RP |
2019 |
80,000 |
Columns of HPLC |
Working |
Publications
List of SCI Publications under Project
|
Authors name |
Title of paper |
Journal Name |
Volume no. |
Page no. |
Year |
DOI |
|---|---|---|---|---|---|---|
|
Nosran A, Kaur P, Randhawa V, Chhibber S, Singh V, Harjai K. |
Design, synthesis, molecular docking, anti-quorum sensing, and anti-biofilm activity of pyochelin-zingerone conjugate |
Drug Development Research |
82(4) |
605-615 |
2021 |
https://doi.org/10.1002/ddr.21781 |
Output/Outcome of the Project
Output/Outcome of the project
This work illustrates the conjugation of pyochelin, a siderophore of P. aeruginosa with dietary phytochemical, zingerone, known for its anti-virulent activity. This conjugate was designed to act as a Trojan Horse for targeted drug delivery exploiting bacterial iron acquisition pathway. The pyochelin-zingerone conjugate was efficiently synthesized using a hydrolysable ester linker which showed iron chelation activity along with significant increase in anti-QS, anti-virulence and antibiofilm activity. Molecular docking studies suggested that conjugate can interact with FptA, a outer membrane receptor of pyochelin with good binding affinity. PZC was also found to be safe with no cytotoxicity for macrophages. Further therapeutic in vivo ability of PZC in peritonitis model, indicated that it has the potential for treating liver infection caused by P. aeruginosa.