Insight into DNA Gyrase inhibition using quantitative structure-Activity relationships and structure-based drug design approaches
Batna Journal of Medical Sciences (online)
; 9(2): 53-56, 2022. figures, tables
Article
ي En
| AIM
| ID: biblio-1412158
المكتبة المسؤولة:
CG1.1
ABSTRACT
The emergence of certain bacterial strains resistant to antibiotics has become a major public health problem, hence the need to develop new antibiotic molecules. Bacterial DNA gyrase, a type II DNA topoisomerase found in all bacteria is a proven target for antibacterial chemotherapy. Our objective is designing novel DNA Gyrase inhibitors using Quantitative StructureActivity Relationships and Structure-Based Drug Design Approaches. We used bioinformatics tools, biological databases like PDB (Protein DataBank), Binding Databases and software's like, MarvinView, MarvinSketch, PyMOL, AutoDockTools-1.5.6. The 3D crystal structure of DNA Gyrase was extracted from PDB (code 4DHU) and we characterized the active site. Using 83 compounds with different Ki were extracted from Binding Databases, we built and validated a QSAR Model (PLS regression) and we confirmed the interesting correlation between predicted and experimental Ki (R2=0,843). Four molecules were chosen to be docked into DNA Gyrase active site using AutoDockTools. The compound which has the low Ki (Benzimidazole urea analogue 5) shows more binding affinity with score value of ΔG= -8,6 kcal/mol than the others compounds. So, it would be very interesting to synthesis this promising compound and to test in vitro its antibacterial properties.
الموضوعات
النص الكامل:
1
الفهرس:
AIM
الموضوع الرئيسي:
DNA, Bacterial
/
Drug Design
/
DNA Gyrase
نوع الدراسة:
Prognostic_studies
اللغة:
En
مجلة:
Batna Journal of Medical Sciences (online)
السنة:
2022
نوع:
Article