Combinatorial Synthesis toward the Discovery of Highly Cytotoxic Fe(III) Complexes DOI

Felix Niemeier,

Lisa-Marie Servos,

Zisis Papadopoulos

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

Cancer remains one of the deadliest diseases worldwide, with some tumors proving difficult to treat and increasingly resistant current therapies. Capitalizing on this, there is a need for new therapeutic agents novel mechanisms action. Among promising candidates, Fe(III) complexes have gained significant attention as potential chemotherapeutic agents. However, research these compounds has been limited small number, leading inefficiencies in drug discovery. This study addresses limitations by developing combinatorial library 495 synthesized from aminophenol, hydroxybenzaldehyde, pyridine derivatives. The were screened cytotoxicity against human breast adenocarcinoma noncancerous fibroblasts, identifying class modest cancer cell selectivity. lead compound effectively eradicated tumor spheroids at low micromolar concentrations, highlighting this approach rapid

Language: Английский

Challenges and applications of artificial intelligence in infectious diseases and antimicrobial resistance DOI Creative Commons
Angela Cesaro, Samuel C. Hoffman, Payel Das

et al.

npj Antimicrobials and Resistance, Journal Year: 2025, Volume and Issue: 3(1)

Published: Jan. 7, 2025

Artificial intelligence (AI) has transformed infectious disease control, enhancing rapid diagnosis and antibiotic discovery. While conventional tests delay diagnosis, AI-driven methods like machine learning deep assist in pathogen detection, resistance prediction, drug These tools improve stewardship identify effective compounds such as antimicrobial peptides small molecules. This review explores AI applications diagnostics, therapy, discovery, emphasizing both strengths areas needing improvement.

Language: Английский

Citations

9
Progress of machine learning in the application of small molecule druggability prediction DOI
Junyao Li, Jianmei Zhang, Rui Guo

et al.

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 285, P. 117269 - 117269

Published: Jan. 10, 2025

Language: Английский

Citations

2
A Cyclometalated Ruthenium(II) Complex Induces Oncosis for Synergistic Activation of Innate and Adaptive Immunity DOI
Tao Feng, Zixin Tang, Jun Shu

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(31)

Published: May 21, 2024

Abstract An optimal cancer chemotherapy regimen should effectively address the drug resistance of tumors while eliciting antitumor‐immune responses. Research has shown that non‐apoptotic cell death, such as pyroptosis and ferroptosis, can enhance immune response. Despite this, there been limited investigation reporting on mechanisms oncosis its correlation with Herein, we designed synthesized a Ru(II) complex targeted nucleus mitochondria to induce oncosis. Briefly, disrupts DNA, which active polyADP‐ribose polymerase 1, accompanied by ATP consumption porimin activation. Concurrently, mitochondrial damage endoplasmic reticulum stress result in release Ca 2+ ions increased expression Calpain 1. Subsequently, specific pore proteins 1 promote cristae destruction or vacuolation, ultimately leading membrane rupture. The analysis RNA sequencing demonstrates initiate oncosis‐associated pathway activate both innate adaptive immunity. In vivo experiments have confirmed promotes dendritic maturation awakens cytotoxic T lymphocytes but also activates inducing polarization macrophages towards an M1 phenotype.

Language: Английский

Citations

13
Metal-Based Approaches for the Fight against Antimicrobial Resistance: Mechanisms, Opportunities, and Challenges DOI Creative Commons
Chenyuan Wang, Xueying Wei, Liang Zhong

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

The rapid emergency and spread of antimicrobial-resistant (AMR) bacteria the lack new antibiotics being developed pose serious threats to global healthcare system. Therefore, development more effective therapies overcome AMR is highly desirable. Metal ions have a long history serving as antimicrobial agents, metal-based compounds are now attracting interest from scientific communities in fight against owing their unique mechanism. Moreover, they may also serve antibiotic adjuvants enhance efficacy clinically used antibiotics. In this perspective, we highlight important showcase studies last 10 years on strategies crisis. Specifically, categorize these metallo-antimicrobials into five classes based modes action (i.e., metallo-enzymes metal-binding enzyme inhibitors, membrane perturbants, uptake/efflux system inhibitors/regulators, persisters oxidative stress inducers). significant advantages over traditional lie multitargeted mechanisms, which render less likelihood generate resistance. However, notice that such raise concern potential side effects low selectivity toward pathogens host, appears be biggest obstacle for downstream translational research. We anticipate combination therapy through repurposing (metallo)drugs with optimization absorption route formulation achieve target-oriented delivery will powerful way combat AMR. Despite challenges, hold great opportunities therapeutic intervention infection by resistant bacteria.

Language: Английский

Citations

2
Leveraging machine learning to streamline the development of liposomal drug delivery systems DOI Creative Commons
Remo Eugster, Markus Orsi,

Giorgio Buttitta

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 376, P. 1025 - 1038

Published: Nov. 8, 2024

Drug delivery systems efficiently and safely administer therapeutic agents to specific body sites. Liposomes, spherical vesicles made of phospholipid bilayers, have become a powerful tool in this field, especially with the rise microfluidic manufacturing during COVID-19 pandemic. Despite its efficiency, liposomal production poses challenges, often requiring laborious, optimization on case-by-case basis. This is due lack comprehensive understanding robust methodologies, compounded by limited data varying lipids. Artificial intelligence offers promise predicting lipid behaviour production, still unexploited potential streamlining development. Herein we employ machine learning predict critical quality attributes process parameters for microfluidic-based liposome production. Validated models formation, size, parameters, significantly advancing our behaviour. Extensive model analysis enhanced interpretability investigated underlying mechanisms, supporting transition Unlocking drug development can accelerate pharmaceutical innovation, making more adaptable accessible.

Language: Английский

Citations

5
IrCytoToxDB: a dataset of iridium(III) complexes cytotoxicities against various cell lines DOI Creative Commons
L.V. Krasnov, Sergei V. Tatarin, Daniil Smirnov

et al.

Scientific Data, Journal Year: 2024, Volume and Issue: 11(1)

Published: Aug. 10, 2024

Iridium(III) complexes nowadays became rising stars in various health-related applications. Thus, there is a necessity to assess cytotoxicity of the synthesized molecules against cancer/normal cell lines. In this report, we present dataset 2694 experimental values 803 iridium 127 different We specify conditions and provide representation machine-readable format. The provides starting point for exploration new iridium-based cellular probes opens possibilities predictions toxicities data-driven generation organometallic anticancer agents.

Language: Английский

Citations

4
Discovery of Phototoxic Metal Complexes with Antibacterial Properties via a Combinatorial Approach DOI Creative Commons
Timothy Kench,

N Chowdhury,

Khondaker Miraz Rahman

et al.

Inorganic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 28, 2025

Antimicrobial resistance is one of the biggest global healthcare challenges. Therefore, there an urgent need to develop new molecules that display distinct antibacterial properties overcome resistance. With this aim, we have developed a combinatorial and semiautomated platform synthesize screen library 78 compounds against Gram-positive Gram-negative bacteria. This based on octahedral iridium(III) complexes with general formula [Ir(CN)2(NN)]Cl (where CN are cyclometallating polyaromatic ligands NN phenanthroline-imidazole or dipyridophenazine derivatives) which known generate reactive oxygen species (ROS) upon light irradiation. From initial entire (in dark under irradiation) Escherichia coli Staphylococcus aureus, show scaffold highly effective at inhibiting growth bacteria intermediate dose (16 μg/mL), displaying hit rate >30% in rising 56% Six were selected for further studies panel five strains, allowing us identify two lead MICs as low 2 μg/mL. These studied more detail establish their mode action using time-kill study S. aureus USA300 strain.

Language: Английский

Citations

0
Chiral Intelligence: The Artificial Intelligence‐Driven Future of Chiroptical Properties DOI

Rafael G. Uceda,

Alfonso Gijón, Sandra Míguez‐Lago

et al.

ChemPhotoChem, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Chirality plays a fundamental role in molecular sciences, with chiroptical properties offering valuable insights into the interaction between chiral molecules and polarized light. Designing materials enhanced requires deep understanding of underlying physical principles, often revealed only through large datasets. In this context, artificial intelligence (AI) emerges as powerful tool for accelerating discovery optimization, efficiently exploring vast chemical spaces. This work explores synergy AI properties, highlighting recent advances data‐driven approaches circular dichroism circularly luminescence. has demonstrated its ability to predict these phenomena accurately while uncovering structure–property relationships that can remain hidden under traditional methods. Various strategies are examined integrating challenges future directions field discussed. conclusion, combining intuition offers great potential rational design next‐generation materials. integration not promises unlock novel compounds but also provides new opportunities deepen our phenomena.

Language: Английский

Citations

0
Advancing super-resolution microscopy with metal complexes: functional imaging agents for nanoscale visualization DOI

Nur Aininie Yusoh,

Martin R. Gill, Xiaohe Tian

et al.

Chemical Society Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

This review highlights recent advancements in the use of metal complexes as functional imaging agents for nanoscale via super-resolution microscopy.

Language: Английский

Citations

0
AttenGpKa: A Universal Predictor of Solvation Acidity Using Graph Neural Network and Molecular Topology DOI
Hongle An, Xuyang Liu, Wensheng Cai

et al.

Journal of Chemical Information and Modeling, Journal Year: 2024, Volume and Issue: 64(14), P. 5480 - 5491

Published: July 10, 2024

Rapid and accurate calculation of acid dissociation constant (p

Language: Английский

Citations

2