Chalcone Derivatives as Potential Inhibitors of P-Glycoprotein and NorA: An In Silico and In Vitro Study.
Minh-Tri LeDieu-Thuong Thi TrinhTrieu-Du NgoViet-Khoa Tran-NguyenDac-Nhan NguyenTung HoangHoang-Minh NguyenTran-Giang-Son DoTan Thanh MaiThanh-Dao TranKhac-Minh ThaiPublished in: BioMed research international (2022)
The human P-glycoprotein (P-gp) and the NorA transporter are the major culprits of multidrug resistance observed in various bacterial strains and cancer cell lines, by extruding drug molecules out of the targeted cells, leading to treatment failures in clinical settings. Inhibiting the activity of these efflux pumps has been a well-known strategy of drug design studies in this regard. In this manuscript, our earlier published machine learning models and homology structures of P-gp and NorA were utilized to screen a chemolibrary of 95 in-house chalcone derivatives, identifying two hit compounds, namely, F88 and F90, as potential modulators of both transporters, whose activity on Staphylococcus aureus strains overexpressing NorA and resistant to ciprofloxacin was subsequently confirmed. The findings of this study are expected to guide future research towards developing novel potent chalconic inhibitors of P-gp and/or NorA.
Keyphrases
- machine learning
- staphylococcus aureus
- escherichia coli
- small molecule
- induced apoptosis
- squamous cell carcinoma
- risk assessment
- signaling pathway
- artificial intelligence
- cell death
- high throughput
- young adults
- cancer therapy
- high resolution
- cell cycle arrest
- endoplasmic reticulum stress
- big data
- drug delivery
- biofilm formation
- lymph node metastasis
- case control