Article
Chemistry, Medicinal
Flavia F. Silveira, Juliana O. de Souza, Lucas V. B. Hoelz, Vinicius R. Campos, Valquiria A. P. Jabor, Anna C. C. Aguiar, M. Cristina Nonato, Magaly G. Albuquerque, Rafael V. C. Guido, Nubia Boechat, Luiz C. S. Pinheiro
Summary: In this study, 35 new compounds were designed and synthesized as inhibitors of P. falciparum, with 30 showing strong anti-parasitic activity and potential as new lead compounds for antimalarial drug discovery.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Arne Alder, Cecilia P. Sanchez, Matthew R. G. Russell, Lucy M. Collinson, Michael Lanzer, Michael J. Blackman, Tim-Wolf Gilberger, Joachim M. Matz
Summary: Malaria parasites use a complex to acidify the digestive vacuole and degrade host erythrocyte hemoglobin, which is essential for their survival in the human bloodstream.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Chemistry, Medicinal
Caroline de Souza Pereira, Helenita Costa Quadros, Diogo Rodrigo Magalhaes Moreira, William Castro, Romulo Ivisson Santos De Deus Da Silva, Milena Botelho Pereira Soares, Diana Fontinha, Miguel Prudencio, Vinicius Schmitz, Helio F. Dos Santos, Mathieu Gendrot, Isabelle Fonta, Joel Mosnier, Bruno Pradines, Maribel Navarro
Summary: The study presented a novel metallic hybrid antimalarial agent with potential dual efficacy in multiple erythrocytic stages of Plasmodium parasites. This hybrid compound showed promising in vitro and in vivo antimalarial activity against both blood and liver stages of the parasites, indicating its potential as a new chemotherapeutic agent for malaria treatment, prevention, and transmission.
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)
Review
Biochemistry & Molecular Biology
Dawid J. Kucharski, Michalina K. Jaszczak, Przemyslaw J. Boratynski
Summary: Late-stage modification of drug molecules is a fast method to increase diversity in already biologically active scaffolds. This review summarizes the modification sites and reactivity types of analogs of mefloquine, chloroquine, and hydroxychloroquine synthesized from readily available active pharmaceutical ingredients (API). The introduction of simple groups and functionalities, as well as coupling with other drugs, polymers, or carriers, resulted in hybrid compounds or conjugates with easily hydrolyzable or more chemically inert bonds. Some of these compounds were tested in antiprotozoal, antibacterial, and antiproliferative assays, as well as enantiodifferentiation experiments.
Article
Infectious Diseases
Nicholas J. White, Francois H. Nosten
Summary: The ideal anti-malarial drug is one that cures all malaria in a single dose, but this demanding aspirational target may have hindered drug development. Therefore, aiming for three-day regimens as in current anti-malarial treatments may be more practical.
Article
Microbiology
Laurent Dembele, Jean-Francois Franetich, Valerie Soulard, Nadia Amanzougaghene, Shahin Tajeri, Teun Bousema, Geert-Jan van Gemert, Roger Le Grand, Nathalie Dereuddre-Bosquet, J. Kevin Baird, Dominique Mazier, Georges Snounou
Summary: This study found that chloroquine can potentiate the activity of 8-aminoquinoline compound primaquine against several malarial parasites in normal primary hepatocytes, but not in a hepatocarcinoma cell line.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Plant Sciences
Gervais Mouthe Happi, Pamela Kemda Nangmo, Liliane Clotide Dzouemo, Sorelle Fotsing Kache, Ariane Dolly Kenmogne Kouam, Jean Duplex Wansi
Summary: Meliaceae plants are important herbal sources for treating malaria in traditional African medicine. Studies have found significant antiplasmodial and insecticidal activities in this plant family, suggesting their potential as eco-friendly pesticides.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Article
Immunology
Sungano Mharakurwa, Zvifadzo Matsena-Zingoni, Nobert Mudare, Charmaine Matimba, Tanatswa Xuxa Gara, Aramu Makuwaza, Gladys Maponga, Shungu Munyati, Lovemore Gwanzura, Susan L. Mutambu, Peter Mason, Tamaki Kobayashi, Nicholas Midzi, William J. Moss, Matthew M. Ippolito
Summary: The removal of chloroquine from national malaria formularies can lead to a decrease in chloroquine-resistant Plasmodium falciparum, highlighting the significant impact of drug policy on antimalarial resistance in malaria control programs.
JOURNAL OF INFECTIOUS DISEASES
(2021)
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
Biology
Ghulam R. Awab, Fahima Aaram, Natsuda Jamornthanyawat, Kanokon Suwannasin, Watcharee Pagornrat, James A. Watson, Charles J. Woodrow, Arjen M. Dondorp, Nicholas P. J. Day, Mallika Imwong, Nicholas J. White
Summary: Within the Pashtun population, the G6PD Med genotype confers a significant protective effect against acute vivax malaria. Through Bayesian statistical modeling, it was found that G6PD Med reduces the incidence of symptomatic P. vivax malaria in both males and females patients.
Article
Pharmacology & Pharmacy
Anne Cristine Almeida, Anna Beatriz Ribeiro Elias, Maria Paula Marques, Gisely Cardoso de Melo, Allyson Guimaraes da Costa, Erick Frota Gomes Figueiredo, Larissa Wanderley Brasil, Fernanda Rodrigues-Soares, Wuelton Marcelo Monteiro, Marcus Vinicius Guimaraes de Lacerda, Vera Lucia Lanchote, Guilherme Suarez-Kurtz
Summary: The study investigated the impact of Plasmodium vivax malaria and chloroquine-primaquine chemotherapy on CYP2D6 and CYP2C19 activity in patients from the Brazilian Amazon. Results showed alterations in CYP2D6 and CYP2C19 metabolic phenotypes, potentially due to changes in pharmacokinetics and cytokine levels during different stages of vivax malaria illness and treatment.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Microbiology
Rebecca de Abreu-Fernandes, Natalia Ketrin Almeida-de-Oliveira, Bianca Ervatti Gama, Larissa Rodrigues Gomes, Aline Rosa De Lavigne Mello, Lucas Tavares de Queiroz, Jacqueline de Aguiar Barros, Maria das Gracas Costa Alecrim, Rodrigo Medeiros de Souza, Lilian Rose Pratt-Riccio, Patricia Brasil, Claudio Tadeu Daniel-Ribeiro, Maria de Fatima Ferreira-da-Cruz
Summary: This study aimed to investigate SNPs in the P. falciparum gene associated with chloroquine (CQ) chemoresistance. By collecting samples from the Amazonas and Acre states from 2010 to 2018, the study found that majority of the samples carried CQ-resistant genotypes, indicating that CQ cannot be reintroduced in malaria therapy.
Review
Chemistry, Medicinal
Pinky Gehlot, Vivek K. Vyas
Summary: Pyrimidine nucleotides are crucial for parasite growth and replication, with parasites having only a de novo pathway for their biosynthesis. The enzyme dihydroorotate dehydrogenase (DHODH) plays a key role in this process and is a target for the discovery of new antimalarial agents. The development of species-selective PfDHODH inhibitors has shown promise in inhibiting parasite growth without affecting normal human functions, providing a potential avenue for the development of novel antimalarial agents.
EXPERT OPINION ON THERAPEUTIC PATENTS
(2023)
Article
Biochemistry & Molecular Biology
Jessica Correa Bezerra Bellei, Nicolas Glanzmann, Barbara Albuquerque Carpinter, Daniela Chaves Renhe, Carolina Brandi Marques, Marina Rocha Azevedo, Livia Maria Barreto, Vinicius Novaes Rocha, Isabelle Karine da Costa Nunes, Henrique Marcelo Gualberto Pereira, Elaine Soares Coimbra, Eduardo Antonio Ferraz Coelho, Adilson David da Silva, Fernando de Pilla Varotti, Kezia Katiani Gorza Scopel
Summary: Chloroquine remains the most effective drug for malaria treatment, although resistance to it has emerged. This study focuses on the synthesis of quinoline derivatives to develop new antimalarials. Compound 3 showed promising activity against malaria, inhibiting parasite growth and protecting against severe malaria development.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Chemistry, Organic
Luiz Claudio Ferreira Pimentel, Lucas Villas Boas Hoelz, Henayle Fernandes Canzian, Frederico Silva Castelo Branco, Andressa Paula de Oliveira, Vinicius Rangel Campos, Floriano Paes Silva Junior, Rafael Ferreira Dantas, Jackson Antonio Lamounier Camargos Resende, Anna Claudia Cunha, Nubia Boechat, Monica Macedo Bastos
Summary: New potential competitive inhibitors targeting the enzyme tyrosine kinase BCR-Abl-1 were synthesized and evaluated for their inhibitory activities against chronic myeloid leukemia. Three compounds showed promising results with IC50 values between 1.0 and 7.3 mu M, suggesting a competitive inhibition mechanism shared with imatinib. One compound exhibited the highest interaction affinity for BCR-Abl-1 in molecular docking studies.
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Biochemical Research Methods
Marcos Martins Gouvea, Renata Correa de Carvalho, Frederico Silva Castelo-Branco, Nubia Boechat, Annibal Duarte Pereira Netto, Flavia Ferreira de Carvalho Marques
Summary: This study evaluated the cleavage characteristics of previously developed isoniazid derivatives through kinetic studies and compared their rates with the respective activities against M. tuberculosis. The results showed that higher cleavage rates are associated with greater activities against M. tuberculosis.
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Andressa Oliveira, Stefany Moura, Luiz Pimentel, Joao Neto, Rafael Dantas, Floriano Silva-Jr, Monica Bastos, Nubia Boechat
Summary: This study synthesized ten novel analogs containing isatins and the phenylamino-pyrimidine pyridine (PAPP) skeleton and evaluated their antiproliferative ability. The results suggest that several of these analogs exhibit stronger inhibitory effects against lung cancer and can be used as prototypes for the development of more effective anti-lung cancer drugs.
Article
Biochemistry & Molecular Biology
Caroline Rodrigues Chaves dos Reis, Hellen Valerio Chaves Moura de Souza, Rennan Papaleo Paes Leme, Frederico Silva Castelo-Branco, Tacio Vinicio Amorim Fernandes, Nubia Boechat, Luiza Rosaria Sousa Dias, Lucas Villas oas Hoelz
Summary: This study investigates the molecular mechanism of benzimidazole compounds as cruzain inhibitors through molecular docking and dynamics simulations. The results suggest that these inhibitors bind to cruzain through steric and hydrogen bonding interactions without altering its structure and compactness.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Review
Chemistry, Medicinal
Luiz C. S. Pinheiro, Julio C. Borges, Vinicius R. Campos, Leonardo C. Dantas
Summary: Leprosy, caused by M. leprae, is a neglected tropical disease with effective treatment. However, the high dose MDT and its adverse effects often lead to treatment abandonment. Antimicrobial resistance remains a challenge in leprosy treatment. This article reviews the WHO guidelines and drug synthesis methods for leprosy chemotherapy.
MINI-REVIEWS IN MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Carine Santos, Luiz Pimentel, Henayle Canzian, Andressa Oliveira, Floriano Junior, Rafael Dantas, Lucas Hoelz, Debora Marinho, Anna Cunha, Monica Bastos, Nubia Boechat
Summary: Imatinib is a BCR-ABL inhibitor, but its resistance and toxicity highlight the need for new inhibitors. This study synthesized imatinib derivatives containing quinoline moieties and evaluated their activity against leukemia cells. Compound 2g showed promising activity and could be a potential treatment for chronic myeloid leukemia (CML) patients with acquired resistance to imatinib.
Article
Biochemistry & Molecular Biology
Milene D. Miranda, Otavio Augusto Chaves, Alice S. Rosa, Alexandre R. Azevedo, Luiz Carlos da Silva Pinheiro, Vinicius C. Soares, Suelen S. G. Dias, Juliana L. Abrantes, Alice Maria R. Bernardino, Izabel C. P. Paixao, Thiago Moreno L. Souza, Carlos Frederico L. Fontes
Summary: This study investigated the effects of N-heterocyclic compounds on HSV-1 replication and found that they can inhibit the replication of the virus, suggesting their potential as antiviral agents.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Jessica V. Faria, Fernanda P. Z. Passos, Paulo H. A. da Costa, Andressa P. de Oliveira, Yasmin O. D. da Cruz, Frederico S. Castelo-Branco, Maria C. S. Lourenco, Silvane M. F. Murta, Policarpo A. S. Junior, Alice M. R. Bernardino, Monica M. Bastos, Nubia Boechat
Summary: This study designed and synthesized two new series of compounds and evaluated their activities against Chagas disease and tuberculosis. The results showed that one of the compounds had important activity against both diseases. This study reinforces the importance of this compound in antimicrobial activity and provides a starting point for the development of new drugs.
MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Gianna Giacoletti, Tatum Price, Lucas V. B. Hoelz, Abdulwhab Shremo Msdi, Samantha Cossin, Katerina Vazquez-Falto, Tacio V. Amorim Fernandes, Vinicius Santos de Pontes, Hongbing Wang, Nubia Boechat, Adwoa Nornoo, Tarsis F. Brust
Summary: In this study, the AC1-selective inhibitor ST034307 was found to alleviate pain in mouse models without causing analgesic tolerance. While unable to detect ST034307 in the mouse brain, a significant reduction in cAMP concentration was observed in the dorsal root ganglia of the animals. These results indicate that AC1 inhibitors are a promising class of analgesic agents that effectively treat pain without inducing tolerance.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Maria da Conceicao Avelino Dias Bianco, Debora Inacio Leite, Frederico Silva Castelo Branco, Nubia Boechat, Elisa Uliassi, Maria Laura Bolognesi, Monica Macedo Bastos
Summary: The concept of polypharmacology plays an important role in the treatment of AIDS, providing life-saving therapies for millions of people living with HIV through drug combinations, multi-target drugs, and co-drugs. Azidothymidine (AZT) is a widely used starting scaffold for the development of multi-target-directed ligands (MTDLs) with good antiretroviral activity.
Article
Parasitology
Carlos Fernando Araujo-Lima, Rita de Cassia Castro Carvalho, Raiza Brandao Peres, Ludmila Ferreira de Almeida Fiuza, Barbara Verena Dias Galvao, Frederico S. Castelo-Branco, Monica Macedo Bastos, Nubia Boechat, Israel Felzenszwalb, Maria de Nazare Correia Soeiro
Summary: This study evaluated the efficacy, safety, and in silico pharmacokinetic profile of four hybrids of aminoquinolines with AVA against T. cruzi. The hybrids showed effective trypanocidal activity without cardiotoxicity in vitro. However, they were predicted to have hepatotoxicity, and further research is needed to evaluate their potential as antiparasitic agents.
Review
Chemistry, Medicinal
Leonardo C. Dantas, Vinicius R. Campos, Julio C. Borges, Luiz C. S. Pinheiro
Summary: This review suggests that compounds with sulfonamide moiety may serve as inhibitors of P. falciparum carbonic anhydrases, and when linked to other compounds, they could potentiate the activities and be used in the design of new antimalarial drugs.
MINI-REVIEWS IN MEDICINAL CHEMISTRY
(2023)
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.
Article
Chemistry, Medicinal
Carlos Fernando Araujo-Lima, Rita de Cassia Castro Carvalho, Sandra Loureiro Rosario, Debora Inacio Leite, Anna Caroline Campos Aguiar, Lizandra Vitoria de Souza Santos, Julianna Siciliano de Araujo, Kelly Salomao, Carlos Roland Kaiser, Antoniana Ursine Krettli, Monica Macedo Bastos, Claudia Alessandra Fortes Aiub, Maria de Nazare Correia Soeiro, Nubia Boechat, Israel Felzenszwalb
Summary: This study aims to synthesize new drugs with multitarget effects through the combination of pharmacophoric moieties. In the in vitro models of intracellular parasite infection, the newly synthesized compound showed moderate anti-parasitic activity against Trypanosoma cruzi and no genotoxicity in vitro, indicating the potential for further in vivo experiments.
Article
Biochemistry & Molecular Biology
Cheyene Almeida Celestino Menozzi, Rodolfo Rodrigo Florido Franca, Pedro Henrique Luccas, Mayara dos Santos Baptista, Tacio Vinicio Amorim Fernandes, Lucas Villas Boas Hoelz, Policarpo Ademar Sales Junior, Silvane Maria Fonseca Murta, Alvaro Romanha, Barbara Verena Dias Galvao, Marcela de Oliveira Macedo, Alana da Cunha Goldstein, Carlos Fernando Araujo-Lima, Israel Felzenszwalb, Maria Cristina Nonato, Frederico Silva Castelo-Branco, Nubia Boechat
Summary: The study successfully synthesized and evaluated new nitrotriazole analogs as potential candidates for Chagas disease drug development. The compounds showed significant inhibitory effects against Trypanosoma cruzi, with nitrotriazoles being more potent than nitroimidazoles and triazoles. The compounds also demonstrated potential for action via nitroreductase activation, showing no mutagenic potential and a low potential for hepatotoxicity.