Polypharmacological Drug Design Guided by Integrating Phenotypic and Restricted Fragment Docking Strategies DOI
Shang Li, Xinxin Li,

Liangliang Ma

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(23), P. 21049 - 21069

Published: Sept. 19, 2024

Polypharmacological drugs are of great value for treating complex human diseases by the combinative modulation several biological targets. However, multitarget drug design with more than two targets is challenging and generally discovered serendipity. Herein, a restricted fragment docking (RFD) computational method combined phenotypic discovery approach was developed rational polypharmacological design. Via genetic combination studies in microglial phenotype, we first identified novel synergistic effects triple target toward RIPK1, MAP4K4, ALK. Drawing on RFD to explore virtual chemical spaces three pockets, lead compound,

Language: Английский

Quick-thread centrifugal membrane filter (QuT-CMF) for concentrating small-volume samples by nanofiltration/reverse osmosis DOI Creative Commons
Patrícia Henriques,

Sören Hams,

Ana Maria Brites Alves

et al.

Separation and Purification Technology, Journal Year: 2025, Volume and Issue: unknown, P. 132323 - 132323

Published: Feb. 1, 2025

Language: Английский

Citations

0
Novel anti-inflammatory compounds that alleviate experimental autoimmune encephalomyelitis DOI
Mengjiao Sun, Ning Liu, Jing Sun

et al.

Phytomedicine, Journal Year: 2025, Volume and Issue: 139, P. 156544 - 156544

Published: Feb. 28, 2025

Language: Английский

Citations

0
Binding mechanism of pentamidine derivatives with human serum acute phase protein α1-acid glycoprotein DOI Creative Commons
Teresa Żołek, Orsolya Dömötör, Jerzy Żabiński

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 266, P. 131405 - 131405

Published: April 4, 2024

Drug binding and interactions with plasma proteins play a crucial role in determining the efficacy of drug delivery, thus significantly impacting overall pharmacological effect. AGP, second most abundant protein blood circulation, has unique capability to bind drugs transport various compounds. In our present study, for first time, we investigated whether major component acute phase lipocalin human plasma, can pentamidine derivatives known their high activity against fungal pathogen Pneumocystis carinii. This investigation was conducted using integrated spectroscopic techniques computer-based approaches. According results, it concluded that compounds having heteroatoms (-NCH3) aliphatic linker addition Br atom methoxy substituent at C-2 C-6 positions on benzene ring, exhibit strong AGP site. These are identified as potential candidates recognition by this protein. MD studies indicated tested analogues complexed AGPs reach an equilibrium state after 60 ns, suggesting stability complexes. observation further corroborated experimental results. Therefore, exploring interaction mechanism holds promise development bis-benzamidine-designed pharmaceutically important drugs.

Language: Английский

Citations

2
Polypharmacological Drug Design Guided by Integrating Phenotypic and Restricted Fragment Docking Strategies DOI
Shang Li, Xinxin Li,

Liangliang Ma

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(23), P. 21049 - 21069

Published: Sept. 19, 2024

Polypharmacological drugs are of great value for treating complex human diseases by the combinative modulation several biological targets. However, multitarget drug design with more than two targets is challenging and generally discovered serendipity. Herein, a restricted fragment docking (RFD) computational method combined phenotypic discovery approach was developed rational polypharmacological design. Via genetic combination studies in microglial phenotype, we first identified novel synergistic effects triple target toward RIPK1, MAP4K4, ALK. Drawing on RFD to explore virtual chemical spaces three pockets, lead compound,

Language: Английский

Citations

0