Review
Biochemistry & Molecular Biology
Efraim Reyes, Liher Prieto, Andrea Milelli
Summary: The interaction between drugs and chiral counterparts, such as proteins, is the main mechanism. The negative impact of chirality on therapeutic outcomes is well-known. The increasing number of non-racemic chiral drugs on the market highlights the need for safe, economic, and environmentally sustainable synthesis methods.
Article
Biochemical Research Methods
Ricardo Moreira Borges, Fernanda das Neves Costa, Fernanda O. Chagas, Andrew Magno Teixeira, Jaewon Yoon, Marcio Barczyszyn Weiss, Camila Manoel Crnkovic, Alan Cesar Pilon, Bruno C. Garrido, Luz Adriana Betancur, Abel M. Forero, Leonardo Castellanos, Freddy A. Ramos, Monica T. Pupo, Stefan Kuhn
Summary: DAFdiscovery is a pipeline designed to accelerate the annotation and discovery of bioactive compounds by combining mass spectrometry, nuclear magnetic resonance, and bioactivity data and using statistical total correlation spectroscopy and statistical heterospectroscopy calculations. It provides a simple-to-use method for analyzing data from different sources in various situations.
PHYTOCHEMICAL ANALYSIS
(2023)
Review
Pharmacology & Pharmacy
Haifan Gong, Julia Bandura, Guan-Lei Wang, Zhong-Ping Feng, Hong-Shuo Sun
Summary: In recent decades, scientists have been able to isolate medicinal compounds from marine organisms with unique structures and bioactivity, thanks to technological advancements. Xyloketal B, a potent therapeutic compound produced by the mangrove fungus Xylaria sp. from the South China Sea, has been extensively studied in various disease models. It exhibits cytoprotective effects in cardiovascular and neurodegenerative diseases, and shows potential in treating non-alcoholic fatty liver disease and glioblastoma.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Pharmacology & Pharmacy
Tianduanyi Wang, Otto I. Pulkkinen, Tero Aittokallio
Summary: Most drug molecules have the ability to modulate multiple target proteins, which can lead to both therapeutic effects and unwanted side effects. Evaluating the selectivity of a compound is an important factor in drug development and repurposing efforts. Traditional methods for characterizing selectivity fall short in quantifying how selective a compound is against a particular target protein. In this study, we propose an optimization-based selectivity scoring method that allows for the identification of potent and selective compounds against given kinase targets. We demonstrate the effectiveness of this method in finding highly selective compounds in computational experiments using a large-scale kinase inhibitor dataset.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Chemistry, Medicinal
Wendy A. Warr, Marc C. Nicklaus, Christos A. Nicolaou, Matthias Rarey
Summary: Designing new medicines more cheaply and quickly is closely related to exploring chemical space more widely and efficiently. This review focuses on the collection of millions or even billions of enumerated chemical structures, as well as larger chemical spaces that are not fully enumerated. New technologies for searching large libraries and combinatorially in chemical space are discussed, along with space navigation techniques and the impact of autonomous laboratories on synthesis of designed compounds. Challenges and opportunities for the future are summarized.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Pharmacology & Pharmacy
Ellie Esfandiari Nazzaro, Fahad Y. Sabei, Walter K. Vogel, Mohamad Nazari, Katelyn S. Nicholson, Philip R. Gafken, Olena Taratula, Oleh Taratula, Monika A. Davare, Mark Leid
Summary: Ewing's sarcoma is a rare and aggressive cancer of bone and soft tissue characterized by specific chromosomal translocations. Current cytotoxic chemotherapies effectively treat localized disease but can lead to treatment-related morbidities, and the survival rate for patients with relapsed or metastatic disease remains low. A new compound, ML111, was identified through high-throughput screening and showed promising inhibitory effects on Ewing's sarcoma cells in vitro and in vivo, suggesting its potential as a new drug lead for further preclinical studies.
Review
Endocrinology & Metabolism
Safaet Alam, Md. Moklesur Rahman Sarker, Taposhi Nahid Sultana, Md. Nafees Rahman Chowdhury, Mohammad A. Rashid, Nusrat Islam Chaity, Chao Zhao, Jianbo Xiao, Elsayed E. Hafez, Shah Alam Khan, Isa Naina Mohamed
Summary: Diabetes is a chronic condition that significantly impacts people's lives worldwide. The development of resistance and side effects to current antidiabetic drugs necessitates the search for novel treatments. Increasingly, scientists, researchers, and pharmaceutical companies are turning to plants and herbal sources to discover potential bioactive compounds for targeted and less side-effect prone antidiabetic drugs. This review highlights prospective candidates, including isolated phytochemicals and/or plant extracts, that have demonstrated significant antidiabetic potential in in vitro, in vivo, and clinical studies. The mechanisms of action for these bioactive compounds are also discussed, emphasizing their potential for further investigation in the discovery and development of novel antidiabetic therapeutics.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Pharmacology & Pharmacy
Johanna Giovannini, Willy Smeralda, Marie Jouanne, Jana Sopkova-de Oliveira Santos, Marco Catto, Anne Sophie Voisin-Chiret
Summary: Tauopathies are neurodegenerative disorders characterized by the accumulation of abnormal tau protein in the brain, with Alzheimer's disease being the most common form. The pathophysiological mechanisms of AD are still not fully understood, and there is currently no curative treatment available. Therefore, targeting tau protein aggregation has become an important focus for therapeutic approaches.
DRUG DISCOVERY TODAY
(2022)
Article
Chemistry, Multidisciplinary
Bruno Linclau, Zhong Wang, Benjamin Jeffries, Jerome Graton, Rodrigo J. Carbajo, Davy Sinnaeve, Jean-Yves Le Questel, James S. Scott, Elisabetta Chiarparin
Summary: Efficient drug discovery relies on optimizing bioactivity and compound properties such as lipophilicity, guided by efficiency metrics; the use of conformer-specific lipophilicities is a less explored strategy; optimizing lipophilicity values for different conformers can create a novel avenue in drug discovery.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Review
Chemistry, Medicinal
Ri Han, Hongryul Yoon, Gahee Kim, Hyundo Lee, Yoonji Lee
Summary: This review article explores the application of artificial intelligence in medicinal chemistry, specifically focusing on the use of machine learning and deep learning techniques in drug screening and design. Research has shown that artificial intelligence can accelerate the drug discovery process and has great potential in predicting and understanding drug interactions and properties. However, data quality issues and technological constraints remain challenges that require interdisciplinary collaboration to fully realize its potential.
Review
Chemistry, Multidisciplinary
Stephane Perreault, Jayaraman Chandrasekhar, Leena Patel
Summary: Atropisomerism is a type of axial chirality that results in non-superimposable stereoisomers due to hindered rotation. Considering the rotational energy barrier and interconversion rate between atropisomers is important in drug discovery. The introduction of sigma bond with restricted rotation in bioactive molecules can limit the number of accessible conformations and improve their pharmacokinetics/ADME profiles. Recent advances in synthesis, purification, and analysis have enabled the application of atropisomerism in medicinal chemistry.
ACCOUNTS OF CHEMICAL RESEARCH
(2022)
Article
Engineering, Biomedical
Yuval Harris, Hagit Sason, Danna Niezni, Yosi Shamay
Summary: Nanoformulations of small molecule drugs have potential applications in treating various diseases. However, the development process of these formulations is complex and lacks predictability. This study presents a new approach to enhance the stability and drug compatibility of nanoparticles by synthesizing novel dye stabilizers. The results demonstrate the effectiveness of the synthesized stabilizer in improving long-term stability and drug compatibility.
Article
Engineering, Multidisciplinary
Haiqin Wu, Liangmin Wang, Ke Cheng, Dejun Yang, Jian Tang, Guoliang Xue
Summary: This paper proposes two schemes for mobile crowdsensing: a basic privacy-aware TD scheme (BPTD) and a privacy-enhanced TD scheme (PETD). Both schemes comprehensively consider privacy and practicability. BPTD achieves high efficiency by conducting operations on shared data with minimal user-side interactions. PETD provides enhanced privacy protection without relying on user-side involvement, using a partial decryption-based Paillier Cryptosystem and secret sharing. The efficiency of PETD is improved through data packing.
IEEE TRANSACTIONS ON NETWORK SCIENCE AND ENGINEERING
(2022)
Review
Biochemistry & Molecular Biology
Li Shi, Naixia Zhang
Summary: Solution nuclear magnetic resonance (NMR) spectroscopy has proven to be a promising tool in drug discovery, particularly in fragment-based drug discovery (FBDD). With the assistance of NMR techniques, multiple candidate compounds and FDA-approved drugs have been developed from FBDD. NMR has broad applications in different stages of the FBDD process, including fragment library construction, hit generation and validation, hit-to-lead optimization, and elucidation of working mechanisms.
Review
Pharmacology & Pharmacy
Sean Vandersluis, Jennifer C. Reid, Luca Orlando, Mickie Bhatia
Summary: The research highlights the limited success in the clinic of effective drugs for cancer patients, and the need for careful evaluation of high attrition rates in current drug development approaches. A meta-analysis of 2918 clinical studies involving 466 drugs for acute myeloid leukemia (AML) was conducted to determine key shared pre-clinical characteristics that relate to successful or unsuccessful drugs in patients. The recommendation is to use phenotypic drug discovery during pre-clinical development, informing and improving foundational discovery screens and platforms for other cancers.
DRUG DISCOVERY TODAY
(2022)