Article
Chemistry, Medicinal
Kanchan Yadav, Anamika Sharma, Salique Hassan Shaham, Sanoop P. Chandrasekharan, Sandeep Kumar, Anamika Dhami, Hisana Nasreen, Kishor Mohanan, Renu Tripathi
Summary: This study identified a new class of 4-aminoquinoline-trifluormethyltriazoline compounds as potential antiplasmodial agents. The compounds were synthesized through a silver-catalyzed three-component reaction and showed promising antimalarial activity in vitro and in vivo. One compound exhibited a 99.9% decrease in parasitic load and a 40% cure rate in animal studies.
Article
Chemistry, Medicinal
Prisca Lagardere, Romain Mustiere, Nadia Amanzougaghene, Sebastien Hutter, Jean-Francois Franetich, Nadine Azas, Patrice Vanelle, Pierre Verhaeghe, Nicolas Primas, Dominique Mazier, Nicolas Masurier, Vincent Lisowski
Summary: Malaria remains a major global health problem, and the development of drug resistance poses a challenge. A series of 4-substituted thieno[3,2-d]pyrimidines were found to exhibit activity against different stages of the malaria parasite, with the chloro analogue of Gamhepathiopine showing promising activity against both the erythrocytic and hepatic stages.
Review
Chemistry, Medicinal
Sisir Nandi, Bhumika Chauhan, Heena Tarannum, Mayank Kumar Khede
Summary: Polypharmacology refers to drugs that have interactions with multiple targets of a unique disease or many disease pathways. It is greatly appreciated in the treatment of complex diseases such as oncology, CNS disorders, and anti-infectives. The integration of diverse compounds from public databases is used for polypharmacological drug discovery research. The study aims to explore the polypharmacological effects of 4-aminoquinoline drugs in combating malaria, cancer, and tuberculosis.
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Melanie Fonte, Natalia Tassi, Diana Fontinha, Ines Bouzon-Arnaiz, Ricardo Ferraz, Maria J. Araujo, Xavier Fernandez-Busquets, Miguel Prudencio, Paula Gomes, Catia Teixeira
Summary: Two novel acridine-based compound families, combining features of primaquine and chloroquine, have shown dual-stage antiplasmodial activity against both chloroquine-sensitive and -resistant Plasmodium falciparum strains, as well as against Plasmodium berghei.
Article
Pharmacology & Pharmacy
Francisco Flavio Vieira de Assis, Jose Sousa de Almeida Junior, Tania Mara Pires Moraes, Fernando de Pilla Varotti, Camila Castilho Moraes, Adilson Sartoratto, Waldiney Pires Moraes, Antonio Humberto Hamad Minervino
Summary: This study evaluated the in vitro antimalarial activity and cytotoxicity of the hydroalcoholic extract of Juca (Libidibia ferrea). The results showed that the Juca extract exhibited significant antimalarial activity and no significant cytotoxicity.
Article
Multidisciplinary Sciences
Nurfarahanim Muhammad Zubir, Mohd Ridzuan Mohd Abd Razak, Amatul Hamizah Ali, Mukram Mohamed Mackeen, Nurul Izzaty Hassan
Summary: The emergence of parasitic strains resistant to most antimalarial drugs has led to the exploration of more effective alternative mechanisms. Hybridization, particularly using the 4-aminoquinoline framework, has shown promise in the development of new antimalarial agents. However, further development and clinical trials are needed for these hybrids, and the lack of detailed preclinical data has hindered progress.
Article
Chemistry, Medicinal
Satoshi Mizuta, Farhana Mosaddeque, Mya Myat Ngwe Tun, Awet Alem Teklemichael, Mayumi Taniguchi, Masashi Hosokawa, Tomoko Yamaguchi, Juliann Makau, Nguyen Tien Huy, Shusaku Mizukami, Noriyuki Nishida, Kouichi Morita, Kenji Hirayama
Summary: We have modified the terminal amino group of N-1-(7-chloroquinolin-4-yl) butane-1,4-diamine to synthesize a series of 7-chloro-4-aminoquinoline derivatives and evaluated their potential as anti-malarial and anti-viral agents. Some of these compounds showed promising anti-malarial effects against both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum. In addition, they were tested in vitro against influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Compound 5h, which contained an N-mesityl thiourea group, exhibited significant anti-infectious effects against malaria, IAV, and SARS-CoV-2. These findings provide new insights for the discovery of drugs for malaria prevention and treatment, as well as virus co-infection.
Article
Chemistry, Organic
Debashruti Bandyopadhyay, Annaram Thirupathi, Divya Radhakrishnan, Adyasha Panigrahi, S. Peruncheralathan
Summary: Functionalised 4-amino-2-(methylthio)quinolines were successfully synthesised through triflic acid-mediated N-heteroannulation, demonstrating high chemoselectivity and mild reaction conditions. Additionally, a new double N-heteroannulation process was developed for the synthesis of complex indolo[3,2-c]quinolines from non-heterocyclic precursors. Natural product isocryptolepine was efficiently synthesised in four steps from an acyclic precursor.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Chemistry, Organic
Miao Li, Yaqun Dong, Cong Zhou, Junxue Bai, Jiang Cheng, Jianwei Sun, Song Sun
Summary: The iridium-catalyzed redox-neutral C-2 and C-3 dual C-H functionalization of indoles with nitrones has been developed to provide 7H-indolo[2,3-c]quinolines with high efficiency and regioselectivity. This newly developed reaction features readily available substrates, operational simplicity, broad scope, good to high efficiency, and excellent regioselectivity, which differs from previous methods.
Article
Biochemistry & Molecular Biology
Rogers J. Nyamwihura, Huaisheng Zhang, Jasmine T. Collins, Olamide Crown, Ifedayo Victor Ogungbe
Summary: The study focused on investigating nopol-based quinoline derivatives for their inhibitory activity against Plasmodium falciparum, one of the parasites that cause malaria. The results showed that certain derivatives were moderately active against the asexual blood stage of the parasite but inactive against chloroquine-resistant strains. Future research will focus on exploring the moderately active and selective compounds against different stages of Plasmodium parasites.
Article
Biochemistry & Molecular Biology
Estevao Silveira Grams, Alessandro Silva Ramos, Mauro Neves Muniz, Raoni S. Rambo, Marcia Alberton Perello, Nathalia Sperotto, Laura Calle Gonzalez, Lovaine Silva Duarte, Luiza Galina, Adilio Silva Dadda, Guilherme Arrache Goncalves, Cristiano Valim Bizarro, Luiz Augusto Basso, Pablo Machado
Summary: By synthesizing and evaluating a series of compounds, it was found that two of them exhibited similar antibacterial effects to isoniazid and showed no significant toxicity to host cells. The chemical stability and permeability of these compounds were also assessed.
Article
Chemistry, Medicinal
Tim Van de Walle, Lore Cools, Sven Mangelinckx, Matthias D'hooghe
Summary: Quinoline, a privileged scaffold in medicinal chemistry, plays a central role in antimalarial and anticancer research, but established quinoline-containing antimalarial drugs are facing widespread resistance. On the other hand, there is a growing interest in quinoline compounds as potential anticancer agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Juliane Aparecida Marinho, Daniel Silqueira Martins Guimaraes, Nicolas Glanzmann, Giovana de Almeida Pimentel, Izabelle Karine da Costa Nunes, Henrique Marcelo Gualberto Pereira, Maribel Navarro, Fernando de Pilla Varotti, Adilson David da Silva, Clarice Abramo
Summary: In this study, molecular hybridization techniques were used to produce compound candidates with antiplasmodial activity for treating malaria infections by CQ-resistant strains. The candidates showed low cytotoxicity and selectiveness to parasites, with IQ5 and IQ6 demonstrating significant parasite growth inhibition in vivo. IQ6 also displayed interaction with ferriprotoporphyrin IX similar to CQ, suggesting promising potential for producing molecules with antiplasmodial activity.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Amy E. Wright, Jennifer E. Collins, Bracken Roberts, Jill C. Roberts, Priscilla L. Winder, John K. Reed, Maria Cristina Diaz, Shirley A. Pomponi, Debopam Chakrabarti
Summary: Novel diterpene bebrycin A and known terpene nitenin showed potent antiplasmodial effects against chloroquine-resistant Plasmodium falciparum strain Dd2, with different mechanisms of action at different stages of the intraerythrocytic life cycle of the parasite.
Article
Chemistry, Medicinal
Tatyana Almeida Tavella, Noeli Soares Melo da Silva, Natalie Spillman, Ana Carolina Andrade Vitor Kayano, Gustavo Capatti Cassiano, Adrielle Ayumi Vasconcelos, Antonio Pedro Camargo, Djane Clarys Baia da Silva, Diana Fontinha, Luis Carlos Salazar Alvarez, Leticia Tiburcio Ferreira, Kaira Cristina Peralis Tomaz, Bruno Junior Neves, Ludimila Dias Almeida, Daniel Youssef Bargieri, Marcus Vinicius Guimaraes de Lacerda, Pedro Vitor Lemos Cravo, Per Sunnerhagen, Miguel Prudencio, Carolina Horta Andrade, Stefanie Costa Pinto Lopes, Marcelo Falsarella Carazzolle, Leann Tilley, Elizabeth Bilsland, Julio Cesar Borges, Fabio Trindade Maranhao Costa
Summary: The natural compound violacein affects protein homeostasis in the malaria parasite, resulting in parasite growth inhibition. It could potentially be developed as a new anti-malarial drug due to its effects on the parasite's stress response.
ACS INFECTIOUS DISEASES
(2021)
Article
Neurosciences
Cristina de Mello-Sampayo, Ana Rita Vaz, Sara C. Henriques, Adelaide Fernandes, Fabiana Paradinha, Pedro Florindo, Paulo Faria, Rui Moreira, Dora Brites, Alvaro Lopes
Summary: NEH and Buph are synthetic cathinones that show distinct behavioral effects on mice and differential harmful impacts on human neurons and microglia. NEH induces microglia activation, while Buph causes early apoptosis in microglia. Both drugs exhibit neurotoxicities, with NEH showing unique effects on microglial function.
NEUROTOXICITY RESEARCH
(2021)
Article
Microbiology
Ana Georgina Gomes-Alves, Margarida Duarte, Tania Cruz, Helena Castro, Francisca Lopes, Rui Moreira, Ana S. Ressurreicao, Ana M. Tomas
Summary: Leishmaniasis is a challenging neglected tropical disease that poses a global threat to public health. Current therapies have drawbacks and are increasingly ineffective due to parasite resistance, highlighting the urgent need for more effective, safer, and cheaper drugs. Screening efforts have identified compounds with inhibitory effects on intracellular L. infantum parasites, showing potential for the future development of new antileishmanial agents.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Sara R. Oliveira, Pedro A. Dionisio, Maria M. Gaspar, Maria B. T. Ferreira, Catarina A. B. Rodrigues, Rita G. Pereira, Monica S. Estevao, Maria J. Perry, Rui Moreira, Carlos A. M. Afonso, Joana D. Amaral, Cecilia M. P. Rodrigues
Summary: Parkinson's disease (PD) is a common neurodegenerative disorder characterized by dopaminergic neuronal loss, with necroptosis playing a role in various neurodegenerative diseases including PD. The compound Oxa12 has been identified as a novel inhibitor of necroptosis, showing potential for mitigating PD pathogenesis in vivo through protection against dopaminergic neuronal loss.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Marta Barbosa, Catia Gomes, Catarina Sequeira, Joana Goncalves-Ribeiro, Carolina Campos Pina, Luis A. Carvalho, Rui Moreira, Sandra H. Vaz, Ana Rita Vaz, Dora Brites
Summary: This study investigated the role of miR-146a in ALS astrocytes and found that upregulating miR-146a can alleviate the detrimental effects of astrocytes on neurons and microglia, suggesting miR-146a as a potential therapeutic target for ALS.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Chemistry, Medicinal
Enrico Cadoni, Pedro R. Magalhaes, Rita M. Emidio, Eduarda Mendes, Jorge Vitor, Josue Carvalho, Carla Cruz, Bruno L. Victor, Alexandra Paulo
Summary: The study aims to synthesize analogues of G4 ligand 360A, identify structure-activity relationships, and design other G4-interactive small molecules. Experimental results show that methylation affects the stability and selectivity of compounds towards G4, with compounds having a relative 1,3-position displaying the best G4 stabilization.
Article
Chemistry, Multidisciplinary
Rafael F. A. Gomes, Joao M. J. M. Ravasco, Kessia H. S. Andrade, Jaime A. S. Coelho, Rui Moreira, Rafael Oliveira, Fatima Nogueira, Carlos A. M. Afonso
Summary: In this study, 5-hydroxymethylfurfural (HMF) was identified as a key synthon for preparing highly complex cyclopentenones (CP) via tandem reactions. The synthesis involved the reaction of HMF with external O- and N-nucleophiles in delta-lactone-fused-CPs hotspots. The new enones showed activity against intraerythrocytic Plasmodium falciparum.
Article
Chemistry, Medicinal
Solida Long, Denise Duarte, Carla Carvalho, Rafael Oliveira, Nuno Santarem, Andreia Palmeira, Diana I. S. P. Resende, Artur M. S. Silva, Rui Moreira, Anake Kijjoa, Anabela Cordeiro da Silva, Fatima Nogueira, Emilia Sousa, Madalena M. M. Pinto
Summary: The study explored the antiparasitic potential of pyrazino [2,1-6] quinazoline-3,6-diones containing indole alkaloids against Plasmodium falciparum, Trypanosoma brucei, and Leishmania infantum. Promising hit compounds with species-specific or broad antiparasitic activity were identified, and structure-activity relationships were observed. In silico studies predicted these compounds as possible inhibitors for prolyl-tRNA synthetase both from Plasmodium and Leishmania, indicating their potential for the development of novel and affordable antiparasitic drugs.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Medicinal
Eduarda Mendes, Israa M. Aljnadi, Barbara Bahls, Bruno L. Victor, Alexandra Paulo
Summary: Organic small molecules that can recognize and bind to G-quadruplex and i-Motif nucleic acids have great potential in selective drug development and medical diagnostic nanodevice applications. This article surveys the major achievements in the therapeutic potential of these quadruplex ligands, their binding modes, effects on quadruplex interactions, and explores the opportunities and challenges in drug discovery.
Article
Biochemistry & Molecular Biology
Natalia Aniceto, Vanda Marques, Joana D. Amaral, Patricia A. Serra, Rui Moreira, Cecilia M. P. Rodrigues, Rita C. Guedes
Summary: This study proposes a combined in silico and experimental approach to identify new therapies for Necroptosis. By using docking and machine learning methods, the researchers successfully predicted potential RIPK1 inhibitors. This screening method allows for the exploration of new areas in chemical space quickly and inexpensively, providing efficient starting points for further drug optimization research.
Article
Chemistry, Multidisciplinary
Luis A. R. Carvalho, Breyan Ross, Lorenz Fehr, Oguz Bolgi, Svenja Woehrle, Kenneth M. Lum, David Podlesainski, Andreia C. Vieira, Reiner Kiefersauer, Rita Felix, Tiago Rodrigues, Susana D. Lucas, Olaf Gross, Ruth Geiss-Friedlander, Benjamin F. Cravatt, Robert Huber, Markus Kaiser, Rui Moreira
Summary: Dipeptidyl peptidases 8 and 9 (DPP8/9) have important roles in biological processes and are potential drug targets. This study discovered 4-oxo-beta-lactams as potent DPP8/9 inhibitors using activity-based protein profiling. X-ray crystallography revealed different ligand binding modes for DPP8 and DPP9. The inhibitors showed inhibition at both the target and cellular levels, with the highest reported selectivity index.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Xingui Liu, Alexia F. Kalogeropulou, Sofia Domingos, Nikolai Makukhin, Raja S. Nirujogi, Francois Singh, Natalia Shpiro, Anton Saalfrank, Esther Sammler, Ian G. Ganley, Rui Moreira, Dario R. Alessi, Alessio Ciulli
Summary: This study reports the development of LRRK2 proteolysis targeting chimeras (PROTACs) and the discovery of a degrader XL01126 as an alternative LRRK2-targeting strategy. XL01126 shows fast and potent degradation of LRRK2 in multiple cell lines, high cell permeability, and oral bioavailability, as well as the ability to penetrate the blood-brain barrier in mice.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Editorial Material
Chemistry, Medicinal
Chiara Borsari, Brieuc Matagne, Kristina Goncharenko, Rui Moreira, Yves P. Auberson
Summary: Diversity in science refers to cultivating talent, promoting full inclusion, and enhancing creativity. The European Federation for Medicinal chemistry and Chemical biology (EFMC) actively promotes diversity and equality of opportunity. EFMC pays attention to cultural, geographical, and gender diversity, in order to create a welcoming and stimulating environment for its members.
Article
Biochemistry & Molecular Biology
Susana Rocha, Rita Felix, Maria Joao Valente, Andreia Bento-Silva, Rute Rebelo, Celia Gomes Amorim, Alberto da Nova Araujo, Rui Moreira, Alice Santos-Silva, Maria Conceicao B. S. M. Montenegro
Summary: This study aimed to evaluate the bioactivity and biocompatibility of polysulfone (PSU) hemodialysis (HD) membranes doped with human neutrophil elastase inhibitors (HNEIs). The results showed that all biomaterials were bioactive and hemocompatible. Compared to Sivelestat, both D4L-1 and D4L-2 exhibited stronger inhibitory abilities.
Review
Biochemistry & Molecular Biology
Debora Inacio Leite, Stefany de Castro Bazan Moura, Maria da Conceicao Avelino Dias, Carolina Catta Preta Costa, Gustavo Peixoto Machado, Luiz Claudio Ferreira Pimentel, Frederico Silva Castelo Branco, Rui Moreira, Monica Macedo Bastos, Nubia Boechat
Summary: The human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS). An increase in viral load leads to a decline in T lymphocytes, compromising the immune system. Tuberculosis (TB) is the most common opportunistic disease in HIV-positive patients. Treatment for HIV-TB coinfection is challenging due to drug interactions, toxicity, non-adherence, and resistance. Recent approaches involve using molecules that target multiple distinct sites to improve therapy. This review discusses the importance of multitarget strategies and the development of structural entities for simultaneous treatment of HIV-TB.
Review
Biochemistry & Molecular Biology
Barbara Bahls, Israa M. Aljnadi, Rita Emidio, Eduarda Mendes, Alexandra Paulo
Summary: Cancer is a societal burden that requires innovative approaches due to the toxic side effects and poor selectivity of conventional chemotherapeutic agents. Uncontrolled proliferation of cancer cells is caused by mutations, deletions, or amplifications in genes encoding for proteins that regulate cell growth and division, such as c-MYC. Directly targeting the c-MYC protein has been unsuccessful, but the exploration of G-quadruplex structures in the c-MYC promoter region has shown promise in downregulating the transcription of this oncogene. In this article, we will overview the significant advancements made in the discovery of a new class of anticancer drugs that target G-quadruplexes in the c-MYC promoter of cancer cells.
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
