Review
Pharmacology & Pharmacy
Jingbo Yang, Yiyang Cai, Kairui Zhao, Hongbo Xie, Xiujie Chen
Summary: This review provides a summary and classification of molecular fingerprints, emphasizing their significance in early drug research and development. It serves as a guide for selecting appropriate fingerprints for compounds in drug R&D.
DRUG DISCOVERY TODAY
(2022)
Review
Pharmacology & Pharmacy
Melissa S. Love, Case W. McNamara
Summary: Recent advancements in drug discovery efforts for cryptosporidiosis have been inspired by the challenges posed by the unique biology of Cryptosporidium. Phenotypic-based screens and repositioning of hits from other pathogens have created a pipeline of potential therapeutics for this disease. Improved methodologies in phenotypic assays are facilitating the development of new compounds for clinical testing.
EXPERT OPINION ON DRUG DISCOVERY
(2021)
Article
Oncology
Vladimir Shapovalov, Liliya Kopanitsa, Lavinia-Lorena Pruteanu, Graham Ladds, David S. Bailey
Summary: Glioblastoma remains a challenging cancer with limited treatment options, and future therapies will require personalized approaches targeting aggressive cellular phenotypes. The use of DIGEX has identified genes encoding drug targets and validated effective antiproliferative agents in human GBM cell models. Further research using this method may uncover new therapeutic opportunities and diagnostic strategies for the complex drug response networks in GBM.
Article
Biochemistry & Molecular Biology
Semih Yagci, Mahmut Gozelle, Selen Gozde Kaya, Yesim Ozkan, Ahmet Bugra Aksel, Filiz Bakar-Ates, Yasemin Dundar, Gokcen Eren
Summary: The study focused on hit-to-lead optimization of a potential SIRT1/2 inhibitor, resulting in improved selectivity for SIRT1 and SIRT2 inhibition. The structural modifications also influenced the cytotoxicity of the compounds against MCF-7 human breast cancer cell line, indicating the impact of SIRT1/2 inhibition on cancer cell viability.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Wei Chen, Di Cui, Steven V. Jerome, Mayako Michino, Eelke B. Lenselink, David J. Huggins, Alexandre Beautrait, Jeremie Vendome, Robert Abel, Richard A. Friesner, Lingle Wang
Summary: In the hit identification stage of drug discovery, absolute protein-ligand binding free-energy perturbation (ABFEP) is a theoretically rigorous and accurate method that can greatly improve hit rates in virtual screening. In this work, an implementation of ABFEP method in FEP+ was described and validated using different compounds and protein receptors. The calculated binding free energies showed good correlation with experimental results and demonstrated the usefulness of ABFEP in improving hit rates in virtual screening.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Medicinal
Andrej Emanuel Cotman, Martina Durcik, Davide Benedetto Tiz, Federica Fulgheri, Daniela Secci, Masa Sterle, Stefan Mozina, Ziga Skok, Nace Zidar, Anamarija Zega, Janez Ilas, Lucija Peterlin Masic, Tihomir Tomasic, Diarmaid Hughes, Douglas L. Huseby, Sha Cao, Linnea Garoff, Talia Berruga Fernandez, Paraskevi Giachou, Lisa Crone, Ivailo Simoff, Richard Svensson, Bryndis Birnir, Sergiy V. Korol, Zhe Jin, Francisca Vicente, Maria C. Ramos, Mercedes de la Cruz, Bjorn Glinghammar, Lena Lenhammar, Sara R. Henderson, Julia E. A. Mundy, Anthony Maxwell, Clare E. M. Stevenson, David M. Lawson, Guido V. Janssen, Geert Jan Sterk, Danijel Kikelj
Summary: We have developed compounds that show promising activity against antibiotic-resistant bacteria, Acinetobacter baumannii and Pseudomonas aeruginosa, which are on the WHO priority list. Compound 27, derived from DNA gyrase inhibitor 1, exhibited improved solubility, inhibition of topoisomerase IV, and no cross-resistance to novobiocin. Further optimization steps led to analogs of 27 with improved plasma distribution and retained anti-Gram-negative activity.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Genetics & Heredity
Zhiting Wei, Sheng Zhu, Xiaohan Chen, Chenyu Zhu, Bin Duan, Qi Liu
Summary: Transcriptional phenotypic drug discovery has achieved great success, and various compound perturbation-based data resources, such as connectivity map (CMap) and library of integrated network-based cellular signatures (LINCS), have been presented. Computational strategies fully mining these resources for phenotypic drug discovery have been proposed. Among them, the fundamental issue is to define the proper similarity between transcriptional profiles. To address this issue, the learning-based framework DrSim is developed, which automatically infers similarity instead of defining it. Evaluation on publicly available datasets shows that DrSim outperforms existing methods in drug annotation and repositioning.
GENOMICS PROTEOMICS & BIOINFORMATICS
(2022)
Article
Biology
Hajar Sirous, Giuseppe Campiani, Vincenzo Calderone, Simone Brogi
Summary: HDAC inhibitors have shown potential in reversing cancer-associated epigenetic changes, but the non-selective profile of current inhibitors limits their clinical utility, leading to the search for isoform-selective inhibitors. This study focused on virtual screening for HDAC1 inhibitors, identifying novel benzamide-based analogs with potential inhibitory activity. The computational approach presented in this study offers guidelines for the development of improved benzamide-based derivatives targeting HDAC1 isoform.
COMPUTERS IN BIOLOGY AND MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Wesley G. Cochrane, Patrick R. Fitzgerald, Brian M. Paegel
Summary: This study demonstrates a scalable design and synthesis approach for an antibacterial-like solid-phase DNA-encoded library, and its application in whole-cell cytotoxicity screening against Escherichia coli and Bacillus subtilis. The screening successfully identified two low-micromolar inhibitors of B. subtilis growth and recapitulated known structure-activity relationships of the fluoroquinolone antibacterial class.
ACS CHEMICAL BIOLOGY
(2021)
Article
Chemistry, Medicinal
Gilda Padalino, Nelly El-Sakkary, Lawrence J. Liu, Chenxi Liu, Danielle S. G. Harte, Rachel E. Barnes, Edward Sayers, Josephine Forde-Thomas, Helen Whiteland, Marcella Bassetto, Salvatore Ferla, George Johnson, Arwyn T. Jones, Conor R. Caffrey, Iain Chalmers, Andrea Brancale, Karl F. Hoffmann
Summary: Recent research has identified a promising anti-schistosomal scaffold in the quinoxaline core, which has shown improved activity and selectivity through chemical optimization. This could potentially serve as an urgently needed alternative to praziquantel for assisting in schistosomiasis elimination strategies.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Chemistry, Medicinal
Bhawna Chopra, Ashwani Kumar Dhingra
Summary: Natural products have been used in folklore for centuries for treating various ailments, with plant-derived products recognized as a source of therapeutic agents and structural diversity. After small modifications, natural molecules can offer better pharmacological potential as new molecular entities.
PHYTOTHERAPY RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Yi Feng, Na Wang, Li-Na Wang, Qian-Hui Zhang, Qi Cheng, Quan-Ling Wang, Sheng-Li Niu, Jing Gu, Rong Zeng, Jie Yang, Yi Yuan, Qin Ouyang, Wen-Ting Shi, Chun-Ling Wu, Wei-Long Shang, Peng-Fei Zheng
Summary: A two-year long-term workshop was developed to improve the teaching quality of a research internship curriculum for pharmacy undergraduates. The workshop integrated lessons and experiments into a genuine research project centered around a phenotypic whole-cell screening strategy. Positive feedback from students showed that the workshop provided cutting-edge knowledge and inspired ambition and confidence in drug discovery.
JOURNAL OF CHEMICAL EDUCATION
(2023)
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)
Review
Immunology
Sangmi Oh, Lena Trifonov, Veena D. Yadav, Clifton E. Barry, Helena I. Boshoff
Summary: Despite over two decades since the first genome sequence of Mycobacterium tuberculosis (Mtb) was published, target-based approaches have not yielded successful drugs in clinical testing. Whole-cell screening combined with elucidation of the mechanism of action remains the most effective method for progressing inhibitors into the tuberculosis drug discovery pipeline. This review discusses scaffolds identified in the past decade from screenings of small molecule libraries against Mtb, and describes the pharmacophore through structure-activity relationship studies.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Pau Nadal Rodriguez, Ouldouz Ghashghaei, Andrea Bagan, Carmen Escolano, Rodolfo Lavilla
Summary: This article introduces a synthetic approach for dealing with the structural complexity of molecules, which offers advantages in terms of synthetic economy and the preparation of larger amounts of drugs. The article summarizes the scientific methodology and main results of the research, provides a general appraisal of the current situation, and offers perspectives on future research directions.
Article
Biochemistry & Molecular Biology
Jose L. Medina-Franco, Norberto Sanchez-Cruz, Edgar Lopez-Lopez, Barbara Diaz-Eufracio
Summary: The concept of chemical space is crucial in chemoinformatics, particularly in drug design and discovery. Molecular representation plays a key role in defining chemical space and exploring structure-property relationships. Freely available tools are important for advancing research and education in this field.
JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
(2022)
Article
Chemistry, Medicinal
Timothy B. Dunn, Gustavo M. Seabra, Taewon David Kim, K. Euridice Juarez-Mercado, Chenglong Li, Jose L. Medina-Franco, Ramon Alain Miranda-Quintana
Summary: The quantification of chemical diversity has extensive applications across various fields. With the expansion of chemical libraries, it is crucial to develop efficient methods for quantifying and visualizing the diversity of large-scale chemical libraries. This article introduces a new extended similarity indices method to measure the fingerprint-based diversity of chemical libraries and proposes the Chemical Library Networks (CLNs) framework for visually representing the chemical space of large libraries.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Medicinal
E. Alexis Flores-Padilla, K. Euridice Juarez-Mercado, Jose J. Naveja, Taewon D. Kim, Ramon Alain Miranda-Quintana, Jose L. Medina-Franco
Summary: The importance of epigenetic drug and probe discovery is increasing, aiding in the development of therapeutic treatments and understanding underlying epigenetic mechanisms in biological processes. Through comprehensive analysis of eleven libraries focused on epigenetic targets, guidance is provided for experimental groups working with high-throughput and medium-throughput screening of epigenetic-focused libraries, and as a reference for designing novel focused epigenetic libraries.
MOLECULAR INFORMATICS
(2022)
Article
Chemistry, Medicinal
Edgar Lopez-Lopez, Carlos M. Cerda-Garcia-Rojas, Jose L. Medina-Franco
Summary: Modification of the tubulin-microtubule system has led to effective strategies for cancer treatment. However, many inhibitors of this system are based on limited structural innovation. This study aims to develop a screening protocol for natural products to identify new potential inhibitors of the tubulin-microtubule system.
MOLECULAR INFORMATICS
(2023)
Editorial Material
Chemistry, Multidisciplinary
Juergen Bajorath, Ana L. L. Chavez-Hernandez, Miquel Duran-Frigola, Eli Fernandez-de Gortari, Johann Gasteiger, Edgar Lopez-Lopez, Gerald M. M. Maggiora, Jose L. Medina-Franco, Oscar Mendez-Lucio, Jordi Mestres, Ramon Alain Miranda-Quintana, Tudor I. I. Oprea, Fabien Plisson, Fernando D. D. Prieto-Martinez, Raquel Rodriguez-Perez, Paola Rondon-Villarreal, Fernanda I. I. Saldivar-Gonzalez, Norberto Sanchez-Cruz, Marilia Valli
Summary: The main conclusions of the first Chemoinformatics and Artificial Intelligence Colloquium include discussions on applications, challenges, and opportunities in drug discovery, de novo drug design, ADME-Tox property predictions, organic chemistry, peptides, and antibiotic resistance. The event attracted speakers from industry, academia, and non-for-profit organizations, as well as 1290 students and academics from over 60 countries.
JOURNAL OF CHEMINFORMATICS
(2022)
Article
Biochemistry & Molecular Biology
Edgar Lopez-Lopez, Jose L. Medina-Franco
Summary: Drug-induced liver injury (DILI) is a major obstacle in drug development and approval, with animal models, liver function tests, and chemical properties being crucial for understanding and preventing DILI events. This study implements data fusion to analyze DILI events by considering different criteria simultaneously, highlighting the importance of in vitro and chemical data analysis for improving our understanding of DILI.
Article
Biochemistry & Molecular Biology
Maria C. Cortez-Trejo, Francisco J. Olivas-Aguirre, Elisa Dufoo-Hurtado, Raquel Castaneda-Moreno, Hassan Villegas-Quintero, Jose L. Medina-Franco, Sandra Mendoza, Abraham Wall-Medrano
Summary: The chemical composition, antioxidant capacity, and anticancer potential of pomegranate fruits with different colors were evaluated. Red pomegranate had the highest nutrient content and antioxidant activity, but showed the same cytotoxicity against normal and cancer cells as pink and white pomegranates. Several phytochemicals in pomegranate fruits exhibited anticancer activity. The anticancer potential of pomegranate fruits is dependent on their phenogenotype.
Article
Chemistry, Medicinal
Timothy B. Dunn, Edgar Lopez-Lopez, Taewon David Kim, Jose L. Medina-Franco, Ramon Alain Miranda-Quintana
Summary: "Understanding structure-activity landscapes" emphasizes the importance of the relationship between molecular structure and activity in drug discovery, and highlights the impact of activity cliffs on design and prediction. This study aims to use n-ary indices and the medoid algorithm to rapidly and efficiently quantify the structure-activity landscapes of large compound data sets, and explore the optimal correlations between similarity measures and structure-activity rankings. The applicability of these methods is demonstrated by analyzing 10 compound data sets with pharmaceutical relevance using different fingerprints, similarity indices, and coincidence thresholds.
MOLECULAR INFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Kenneth Lopez-Perez, Edgar Lopez-Lopez, Jose L. Medina-Franco, Ramon Alain Miranda-Quintana
Summary: Visualization of chemical space is crucial in various aspects of chemistry, such as compound library design and exploring structure-property relationships. ChemMaps is a visualization methodology that approximates compound distribution in large datasets based on satellite compounds with a similar mapping. Extended similarity indices are proposed to identify relevant regions and reduce high-dimensional data in describing a library's chemical space.
Review
Biochemistry & Molecular Biology
Cesar A. Zaa, alvaro J. Marcelo, Zhiqiang An, Jose L. Medina-Franco, Marco A. Velasco-Velazquez
Summary: Anthocyanins, a type of flavonoid, possess potent antioxidant properties and can penetrate the blood-brain barrier, exhibiting neuroprotective effects. Including anthocyanin-rich foods in the diet has been shown to lower the risk of neurodegenerative diseases, as their antioxidant, anti-inflammatory, and anti-apoptotic properties contribute to neuroprotection, particularly in Alzheimer's and Parkinson's diseases.
Article
Chemistry, Multidisciplinary
Raziel Cedillo-Gonzalez, Jose L. Medina-Franco
Summary: This study explores, characterizes, and analyzes the chemical space of 409 G9a inhibitors reported in a large public database. It quantifies the structural diversity of G9a inhibitors and compares them with commercial libraries focused on epigenetic targets. The findings will contribute to the development of predictive models for identifying G9a inhibitors and highlight the importance of screening commercial libraries to expand the relevant chemical space.
Article
Chemistry, Medicinal
Alejandro Gomez-Garcia, Daniel A. Acuna Jimenez, William J. Zamora, Haruna L. Barazorda-Ccahuana, Miguel A. Chavez-Fumagalli, Marilia Valli, Adriano D. Andricopulo, Vanderlan da S. Bolzani, Dionisio A. Olmedo, Pablo N. Solis, Marvin J. Nunez, Johny R. Rodriguez Perez, Hoover A. Valencia Sanchez, Hector F. Cortes Hernandez, Jose L. Medina-Franco
Summary: The Latin American Natural Products Database (LANaPDB) is a public compound collection that gathers chemical information of natural products from various databases in Latin America. The current version includes chemical structures from six countries, with terpenoids, phenylpropanoids, and alkaloids being the most abundant compounds. LANaPDB covers a wide chemical space and many compounds exhibit drug-like properties.
Article
Chemistry, Multidisciplinary
Edgar Lopez-Lopez, Oscar Robles, Fabien Plisson, Jose L. Medina-Franco
Summary: Peptide structure-activity/property relationship (P-SA/PR) studies aim to understand how the structural variations of peptides influence their biological activities and other functional properties, accelerating the rational design and optimization of peptide-based drugs, biomaterials, or diagnostic agents. This study used the MAP4 fingerprint to analyze the structure-activity relationship of 223 antimicrobial peptides against methicillin-resistant Staphylococcus aureus (MRSA), identifying critical residues and structural motifs that play a crucial role in the anti-MRSA activity of the peptides.
Review
Chemistry, Multidisciplinary
Conrad V. Simoben, Smith B. Babiaka, Aurelien F. A. Moumbock, Cyril T. Namba-Nzanguim, Donatus Bekindaka Eni, Jose L. Medina-Franco, Stefan Guenther, Fidele Ntie-Kang, Wolfgang Sippl
Summary: The use of traditional medicine has a long history and is still relied upon by many, especially in developing or underprivileged communities. In silico-based methods have played a crucial role in drug discovery, particularly in identifying natural product-based candidates. However, there are challenges in identifying and proposing novel natural product-based hits.
Article
Chemistry, Multidisciplinary
Felipe Victoria-Munoz, Norberto Sanchez-Cruz, Jose L. Medina-Franco, Fabian Lopez-Vallejo
Summary: This study analyzed the structure-activity relationships of transcription factors associated with quorum sensing in P. aeruginosa, identifying structural features such as molecular size and hydrogen bond acceptors that are significant for antagonist activity.
