Review
Biochemistry & Molecular Biology
Beatriz Suay-Garcia, Jose I. Bueso-Bordils, Antonio Falco, Gerardo M. Anton-Fos, Pedro A. Aleman-Lopez
Summary: Traditionally, drug development involved time-consuming and costly processes, but the application of virtual combinatorial chemistry and virtual screening can greatly accelerate the search and development of drugs, while saving costs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Leticia Tiburcio Ferreira, Joyce V. B. Borba, Jose Teofilo Moreira-Filho, Aline Rimoldi, Carolina Horta Andrade, Fabio Trindade Maranhao Costa
Summary: Malaria remains a public health burden in tropical and subtropical areas, with drug-resistant Plasmodium strains driving the exploration of novel antimalarial compounds. Through virtual screening, promising natural compound-based antimalarial molecules can be identified for further development.
Article
Biochemistry & Molecular Biology
Vivek Asati, Sanjay K. Bharti, Ratnesh Das, Varsha Kashaw, Sushil Kumar Kashaw
Summary: The study utilized pharmacophore, 3-D QSAR, docking, and virtual screening to identify potential inhibitors against ALK2 kinase. Through these methods, compounds with good binding interactions with ALK2 kinase were found, suggesting their potential as drug candidates.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Correction
Chemistry, Multidisciplinary
Christine N. Morrison, Kathleen E. Prosser, Ryjul W. Stokes, Anna Cordes, Nils Metzler-Nolte, Seth M. Cohen
Summary: Correction issued for the article titled "Expanding medicinal chemistry into 3D space: metallofragments as 3D scaffolds for fragment-based drug discovery" by Christine N. Morrison et al., Chem. Sci., 2020, 11, 1216-1225, https://doi.org/10.1039/C9SC05586J.
Correction
Chemistry, Multidisciplinary
Christine N. Morrison, Kathleen E. Prosser, Ryjul W. Stokes, Anna Cordes, Nils Metzler-Nolte, Seth M. Cohen
Summary: The study introduces a novel approach using metallofragments as 3D scaffolds for fragment-based drug discovery. This method has great potential in the field of medicinal chemistry and provides a new direction for drug development.
Article
Biochemistry & Molecular Biology
Palanisamy Prakash, Durairaj Vijayasarathi, Kuppusamy Selvam, Sengodan Karthi, Rengarajan Manivasagaperumal
Summary: This study analyzed compounds isolated from Decalepis hamiltonii using molecular docking and virtual screening, identifying a number of potential anti-cancer drug molecules that meet ADME and toxicity parameters. The research may provide clues for discovering novel drug inhibitors with similar activity for cancer properties.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Biochemistry & Molecular Biology
Bhumi M. Shah, Palmi Modi, Priti Trivedi
Summary: Pharmacophore modeling, molecular docking, and in silico ADME studies were conducted to determine the binding mode and drug likeliness profile of Pyrrolidine derivatives as Dipeptidyl peptidase IV inhibitors. A statistically significant 3D-QSAR model was generated, with high correlation and predictive capability, indicating potential for novel drug design.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Biochemistry & Molecular Biology
Hocheol Lim, Hansol Hong, Seonik Hwang, Song Ja Kim, Sung Yum Seo, Kyoung Tai No
Summary: In this study, we identified two potent natural product inhibitors of MMP-9 using a novel quantum mechanical workflow, and demonstrated the potential of this workflow. The inhibitors interact with specific hotspot residues of MMP-9 and possess good binding affinity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Lavanya Nagamalla, J. V. Shanmukha Kumar
Summary: In this study, three non-cancer drugs with good binding energies against AXL kinase were identified through virtual screening and further studied in vitro on breast cancer MCF-7 cell lines. Additionally, QSAR studies on N-[4-(Quinolin-4-yloxy)phenyl]benzenesulfonamides derivatives were conducted to design potent inhibitors for AXL kinase. The resulting QSAR equation had good predictivity and provided valuable insights into the chemical properties of AXL inhibitors for the development of novel inhibitors.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Chemistry, Multidisciplinary
Felix Torres, Matthias Buetikofer, Gabriela R. R. Stadler, Alois Renn, Harindranath Kadavath, Raitis Bobrovs, Kristaps Jaudzems, Roland Riek
Summary: Although nuclear magnetic resonance (NMR) is commonly used in fragment-based drug design, its lack of sensitivity has limited its implementation in high-throughput screening. However, photochemically induced dynamic nuclear polarization (photo-CIDNP) is a promising method that can improve the sensitivity of NMR. This research demonstrates the detection of weak binders using low micromolar concentrations, exploiting the polarization enhancement provided by photo-CIDNP and achieving faster interaction detection compared to standard techniques. Furthermore, an automated flow-through platform and a photo-CIDNP fragment library are presented, providing a comprehensive approach for fragment-based screening.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Cecile Bieri, Akori Esmel, Melalie Keita, Luc Calvin Owono Owono, Brice Dali, Eugene Megnassan, Stanislav Miertus, Vladimir Frecer
Summary: In order to address the cost-effective therapy of neglected and tropical diseases such as malaria, computational design was carried out to discover new inhibitors of Plasmodium falciparum (PfENR). The study developed a QSAR model and a pharmacophore model to predict the inhibitory potencies and generate a virtual combinatorial library of potential inhibitors. Through virtual screening and molecular dynamics, potential new potent inhibitors with predicted antimalarial effects and favorable pharmacokinetic profiles were identified, targeting the novel pharmacological target PfENR.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Vishal Dey, Raghu Machiraju, Xia Ning
Summary: This article introduces a molecular machine learning method TAc and TAc-fc based on transfer learning, which improves the classification performance of target tasks by leveraging source domain data and transferring useful information. The experiments demonstrate that TAc outperforms all baselines on a large number of target tasks, while TAc-fc performs better on some tasks.
Article
Chemistry, Medicinal
Antti Poso
Summary: WRD5 is a promising target for anticancer drug discovery and plays a vital role in epigenetic regulation. PROTACs offer a new option for biological inactivation of WRD5, and new WRD5 targeting PROTACs introduced in a study make it possible to evaluate WRD5 as a drug target.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Chengqian Wei, Junjie Huang, Yu Wang, Yifang Chen, Xin Luo, Shaobo Wang, Zengxue Wu, Jixiang Chen
Summary: A series of new oxadiazole sulfone derivatives containing an amide moiety were synthesized to screen high-efficiency antibacterial agents for rice bacterial diseases. Compound 10 showed excellent antibacterial activity against Xanthomonas oryzae pv. oryzae and Xanthomonas oryzae pv. oryzicola, with EC50 values superior to commercial bactericides. Compound 10 demonstrated superior protective and curative activities against rice bacterial leaf blight and rice bacterial leaf streak compared to other tested compounds. Additionally, compound 10 exhibited potential mechanisms of action by affecting extracellular polysaccharides, cell membranes, and enzyme activity of dihydrolipoamide S-succinyltransferase to inhibit the growth of Xanthomonas oryzae pv. oryzae and Xanthomonas oryzae pv. oryzicola.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Sk. Abdul Amin, Kalyan Ghosh, Shovanlal Gayen, Tarun Jha
Summary: The World Health Organization declared COVID-19 as a global pandemic requiring rapid response; designing inhibitors against SARS-CoV-2 as a starting point for anti-viral drugs; the study integrated different drug design strategies, useful for COVID-19 drug discovery.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Chemistry, Medicinal
Fabio S. Fernandes, Hugo Santos, Samia R. Lima, Caroline Conti, Manoel T. Rodrigues Jr, Lucas A. Zeoly, Leonardo L. G. Ferreira, Renata Krogh, Adriano D. Andricopulo, Fernando Coelho
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Editorial Material
Chemistry, Medicinal
Leonardo L. G. Ferreira, Adriano D. Andricopulo
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2020)
Article
Parasitology
Rogerio P. Xavier, Ana C. Mengarda, Marcos P. Silva, Daniel B. Roquini, Maria C. Salvadori, Fernanda S. Teixeira, Pedro L. Pinto, Thiago R. Morais, Leonardo L. G. Ferreira, Adriano D. Andricopulo, Josue de Moraes
PARASITES & VECTORS
(2020)
Article
Plant Sciences
Airton Damasceno Silva, Alessandra Regina Pepe Ambrozin, Ana Flavia S. de Camargo, Felipe De Paula Nogueira Cruz, Leonardo Luiz Gomes Ferreira, Renata Krogh, Taynara Lopes Silva, Ilana Lopes Baratella da Cunha Camargo, Adriano Defini Andricopulo, Paulo Cezar Vieira
Summary: Fungal cocultivation increases the biological activity of extracts, with some extracts obtained from cocultivation showing activity against Gram-positive and Gram-negative bacteria, as well as Trypanosoma cruzi and Leishmania infantum. Co-cultures containing Fusarium guttiforme produce extracts with the highest activity against Leishmania infantum.
Editorial Material
Chemistry, Medicinal
Leonardo L. G. Ferreira, Adriano D. Andricopulo
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2020)
Article
Oncology
Wanessa F. Altei, Bianca C. Pachane, Lucimara J. Martins, Ralph C. Gomes, Ricardo N. Santos, Daniara C. Fernandes, Heloisa S. Selistre-de-Araujo, Fernando Coelho, Adriano D. Andricopulo
Summary: The study evaluated the potential of eight synthetic spirocyclohexadienones as cell migration inhibitors, with four compounds significantly inhibiting cell migration and highlighting a potential binding at the colchicine binding site in tubulin. The most potent analogs induced apoptosis of tumor cells, suggesting a different mechanism of action for inhibiting cell migration.
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
(2021)
Review
Plant Sciences
Marilia Valli, Leticia Cristina Vieira Atanazio, Gustavo Claro Monteiro, Roberta Ramos Coelho, Daniel Pecoraro Demarque, Adriano Defini Andricopulo, Laila Salmen Espindola, Vanderlan da Silva Bolzani
Summary: Natural products from Brazilian biodiversity, particularly from the Cerrado region, are highlighted as potential sources of active compounds for mosquito control due to the emergence of resistant mosquito populations. Scientific reviews on bioactive natural products are important for providing molecular models and effective measures to reduce the incidence of arboviruses diseases worldwide.
Article
Biochemistry & Molecular Biology
Humberto E. Ortega, Vitor B. Lourenzon, Marc G. Chevrette, Leonardo L. G. Ferreira, Rene F. Ramos Alvarenga, Weilan G. P. Melo, Tiago Venancio, Cameron R. Currie, Adriano D. Andricopulo, Tim S. Bugni, Monica T. Pupo
Summary: Three antifungal macrolides were isolated from Streptomyces sp. ISID311, showing high antagonism against Escovopsis sp. and potent activity against Leishmania donovani. The planar structures were determined by NMR and MS analysis, with stereochemical assignments confirmed by bioinformatic analysis.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Mariana Bastos dos Santos, Beatriz Carvalho Marques, Gabriela Miranda Ayusso, Mayara Aparecida Rocha Garcia, Luana Chiquetto Paracatu, Ivani Pauli, Vanderlan Silva Bolzani, Adriano Defini Andricopulo, Valdecir Farias Ximenes, Maria Luiza Zeraik, Luis Octavio Regasini
Summary: A series of chalcones and their B-aryl analogues were synthesized and evaluated for their inhibitory effects on MPO chlorinating activity. B-thiophenyl chalcone showed inhibition of MPO activity with low toxicity, making it a potential candidate for new non-steroidal anti-inflammatory compounds.
BIOORGANIC CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Hugo Passos Vicari, Keli Lima, Ralph da Costa Gomes, Daniara Cristina Fernandes, Jean Carlos Lipreri da Silva, Manoel Trindade Rodrigues Junior, Aline Silva Barroso de Oliveira, Ricardo Nascimento dos Santos, Adriano Defini Andricopulo, Fernando Coelho, Leticia Veras Costa-Lotufo, Joao Agostinho Machado-Neto
Summary: The study identified a novel synthetic cyclopenta[b]indole compound that exhibited anti-leukemic effects by disrupting microtubule dynamics, presenting a potential therapeutic option for ATRA-resistant APL. This compound showed significant cytotoxic activity in APL cells, decreased clonogenicity, increased apoptosis, and induced cell cycle arrest, indicating its potential as a new antineoplastic agent. In addition, molecular analyses revealed the impact of the compound on gene expression and molecular pathways involved in cell proliferation, apoptosis, and DNA damage.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Infectious Diseases
Rafael Augusto Alves Ferreira, Celso de Oliveira Rezende Junior, Pablo David Grigol Martinez, Paul John Koovits, Bruna Miranda Soares, Leonardo L. G. Ferreira, Simone Michelan-Duarte, Rafael Consolin Chelucci, Adriano D. Andricopulo, Mariana K. Galuppo, Silvia R. B. Uliana, An Matheeussen, Guy Caljon, Louis Maes, Simon Campbell, Jadel M. Kratz, Charles E. Mowbray, Luiz Carlos Dias
Summary: Leishmaniasis is a neglected tropical disease that affects millions of people worldwide. The current drugs for treating this disease have drawbacks such as toxicity and long treatment regimens. Research has identified a promising target molecule, but in vivo tests showed poor efficacy.
PLOS NEGLECTED TROPICAL DISEASES
(2021)
Article
Biochemistry & Molecular Biology
Maria Luiza Zeraik, Ivani Pauli, Luiz A. Dutra, Raquel S. Cruz, Marilia Valli, Luana C. Paracatu, Carolina M. Q. G. de Faria, Valdecir F. Ximenes, Luis O. Regasini, Adriano D. Andricopulo, Vanderlan S. Bolzani
Summary: Two prenyl chalcones were identified as potent inhibitors of LOX-1, with the most active compound showing competitive LOX-1 inhibitory properties. Molecular modeling studies indicated the importance of prenyl moieties for the binding of the inhibitors to the LOX binding site, related to their pharmacological properties.
Article
Biochemistry & Molecular Biology
Alex R. Medeiros, Leonardo L. G. Ferreira, Mariana L. de Souza, Celso de Oliveira Rezende Junior, Rocio Marisol Espinoza-Chavez, Luiz Carlos Dias, Adriano D. Andricopulo
Summary: The study explored the design of cruzain inhibitors based on imidazole scaffolds through molecular docking and quantitative structure-activity relationship analysis. Models were built and key structural properties determining cruzain inhibition were identified, revealing novel insights for the design of improved inhibitors.
Article
Biochemistry & Molecular Biology
Henrique R. Teles, Leonardo L. G. Ferreira, Marilia Valli, Fernando Coelho, Adriano D. Andricopulo
Summary: In this study, 2D- and 4D-quantitative structure-activity relationship (QSAR) models were developed to investigate the activity of a series of oxazole and oxadiazole derivatives against Leishmania infantum, the causative agent of visceral leishmaniasis. A clustering strategy based on structural similarity was used to divide the compounds into two groups, followed by the development of 2D- (R-2 = 0.90, R(2)pred = 0.82) and 4D-QSAR models (R-2 = 0.80, R(2)pred = 0.64) with improved statistical robustness and predictive ability.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Infectious Diseases
Gabriela Marinho Righetto, Jose Luiz de Souza Lopes, Paulo Jose Martins Bispo, Camille Andre, Julia Medeiros Souza, Adriano Defini Andricopulo, Leila Maria Beltramini, Ilana Lopes Baratella da Cunha Camargo
Summary: Antimicrobial resistance is a major public health concern and there is a need for novel antimicrobial therapies. This study designed a new antimicrobial peptide Pln149-PEP20 and tested its activity against 60 different species of bacteria. The results showed that Pln149-PEP20 had excellent bactericidal activity and its target was likely genes associated with membrane metabolism.