Article
Chemistry, Medicinal
Jelena Popovic-Djordjevic, Cristina Quispe, Roberta Giordo, Aleksandar Kostic, Jelena S. Katanic Stankovic, Patrick Valere Tsouh Fokou, Katya Carbone, Miquel Martorell, Manoj Kumar, Gianfranco Pintus, Javad Sharifi-Rad, Anca Oana Docea, Daniela Calina
Summary: This article reviews the latest information on the anti-HIV activity of natural and synthetic compounds, including their history, mechanism of action, and the role of plants and their bioactive compounds as a source of new anti-HIV drugs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Jindra Valentova, Lucia Lintnerova, Natalia Miklasova, Bianka Obonova, Ladislav Habala
Summary: Life is chiral, and the chiral discrimination of molecules plays an important role in medicinal chemistry. Different enantiomers of chiral compounds can have different effects in terms of pharmacodynamics, pharmacokinetics, and toxicity. The use of only one enantiomer can enhance the bioactivity of a drug and reduce adverse effects. This is particularly significant in natural products, as most of them contain chiral centers. This survey discusses the impact of chirality on anticancer chemotherapy and focuses on the recent developments in this area, particularly synthetic derivatives of natural drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Gaurav Gopal Naik, Ankit Uniyal, Deepak Chouhan, Vinod Tiwari, Alakh N. Sahu
Summary: This review discusses the potential of various natural molecules, such as capsaicinoids and curcumin, to activate TRPV1 channels and be used for the treatment of neuropathic pain.
CURRENT PHARMACEUTICAL BIOTECHNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Raul R. Rodriguez-Berrios, Stephen R. Isbel, Alejandro Bugarin
Summary: Polypropionate units, found in many natural products, have antimicrobial and therapeutic potential. This review includes all epoxide-based methodologies developed by research groups such as Kishi, Katsuki, Marashall, Miyashita, Prieto, Sarabia, Jung, McDonald, etc. for the synthesis of polypropionates. The review also includes the isolation and biological activities of synthetized polypropionates and related natural products.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Luis D. Gonzalez-Morales, Adriana Moreno-Rodriguez, Lenci K. Vazquez-Jimenez, Timoteo Delgado-Maldonado, Alfredo Juarez-Saldivar, Eyra Ortiz-Perez, Alma D. Paz-Gonzalez, Edgar E. Lara-Ramirez, Lilian Yepez-Mulia, Patricia Meza, Gildardo Rivera
Summary: Cutaneous leishmaniasis (CL) is a global public health problem without available vaccines and with limited effective treatments. This study performed virtual screening of natural products against Leishmania mexicana using molecular docking, and selected four compounds with promising leishmanicidal activity. The ADME-Tox analysis suggested favorable properties for these compounds, and one of them, S-8, exhibited higher activity than the reference drug glucantime.
Review
Biochemistry & Molecular Biology
Alicja K. Surowiak, Lucyna Balcerzak, Stanislaw Lochynski, Daniel J. Strub
Summary: Terpenoids with lactone moieties are known for their high bioactivity, with artemisinin being a well-known drug against malaria. New terpenoid lactones are considered potential active agents against various diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Cetin Bayrak, Parham Taslimi, Namik Kilinc, Ilhami Gulcin, Abdullah Menzek
Summary: In this study, the natural bromophenol butyl 2-(3,5-dibromo-4-hydroxyphenyl)acetate (1) and indene derivatives 34 and 35 were successfully synthesized. Several known natural bromophenols and their derivatives were also synthesized. The synthesized compounds exhibited strong inhibition effects against acetylcholinesterase, butyrylcholinesterase, and α-glycosidase enzymes.
CHEMISTRY & BIODIVERSITY
(2023)
Article
Chemistry, Multidisciplinary
Julian M. Feilner, Immanuel Plangger, Klaus Wurst, Thomas Magauer
Summary: This study utilized highly functionalized bifunctional alkenes to achieve a polyene tetracyclization, leading to the total synthesis of the tricyclic diterpenoid pimara-15-en-3 alpha-8 alpha-diol. The versatile route also allowed for the preparation of a diverse library of cyclization precursors for the total synthesis of the tetracyclic nor-diterpenoid norflickinflimiod C, providing insights into complex pentacyclic products.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Medicinal
Yong Qu, Tian-Yi Zhou, Feng-Wei Guo, Mei-Yan Wei, Guang-Ying Chen, Yu-Cheng Gu, Chang-Yun Wang, Chang-Lun Shao
Summary: Inflammation is associated with various diseases and there is a need for better anti-inflammatory drugs. This study synthesized and characterized eight enantiopure isomers of yaequinolone alkaloids. The synthesized compounds showed significant anti-inflammatory activities, surpassing the effectiveness of indomethacin. Additionally, certain compounds displayed inhibition of IL-6 production, indicating their potential as new anti-inflammatory agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Prashant Kumar, Pravesh Kumar, Sugumar Venkataramani, S. S. V. Ramasastry
Summary: This study reveals a new chemical reactivity pattern of allylic gem-diacetates and successfully synthesizes complex benzo[f]chromene compounds, demonstrating the versatility of the method. Additionally, interesting photochromic properties of the new classes of benzo[f]chromenes are discovered.
Article
Chemistry, Physical
Prashant Kumar, Pravesh Kumar, Sugumar Venkataramani, S. S. V. Ramasastry
Summary: This work explores the unusual chemical reactivity pattern of allylic gem-diacetates and establishes them as new prototypes for synthesizing complex benzo[f]chromene systems. The versatility of the method in synthesizing bioactive natural products based on chromene is demonstrated, along with the discovery of interesting photochromic properties of the new classes of benzo[f]chromenes.
Review
Biochemistry & Molecular Biology
Samuele Sala, Scott K. Micke, Gavin R. Flematti
Summary: This review focuses on marine natural products found along the Western Australian coastline. Various types of secondary metabolites, including terpenoids, alkaloids, polyketides, fatty acid derivatives, peptides, and arsenic-containing compounds, have been identified through over 40 years of research. Many of these compounds have been reported to exhibit diverse bioactivities. The compound classes and their associated bioactivities from marine organisms found along the Western Australian coastline are described in this article.
Review
Biochemistry & Molecular Biology
Yeqin Yuan, Huizhi Long, Ziwei Zhou, Yuting Fu, Binyuan Jiang
Summary: Breast cancer is the most common cancer in women, with a rising incidence that poses significant challenges for treatment. The PI3K-AKT pathway and its targets play crucial roles in breast cancer development, and natural products and drugs targeting this pathway show potential for treatment. This review discusses the role of the PI3K-AKT signaling pathway in breast cancer and highlights the use of natural products and drugs targeting this pathway in clinical trials.
Article
Infectious Diseases
Flaminia Mazzone, Viktor E. Simons, Lasse van Geelen, Marian Frank, Attila Mandi, Tibor Kurtan, Klaus Pfeffer, Rainer Kalscheuer
Summary: Toxoplasma gondii is a pathogen that can infect various warm-blooded animals, including humans, causing toxoplasmosis. Current treatments for toxoplasmosis have severe side effects and are not effective in eradicating chronic infection. Therefore, there is an urgent need to develop novel anti-toxoplasma drugs with low toxicity. In this study, eight natural products were isolated from the crude extract of the endophytic fungus Paraboeremia selaginellae obtained from the leaves of the plant Philodendron monstera. Six of these natural products showed antitoxoplasma activity with low or no cytotoxicity in human cell lines. These findings suggest that biphenyl ethers, bioxanthracenes, and 5S,6S-phomalactone from P. selaginellae are potential candidates for novel anti-toxoplasma drugs.
Article
Multidisciplinary Sciences
Suzie K. Hight, Trevor N. Clark, Kenji L. Kurita, Elizabeth A. McMillan, Walter Bray, Anam F. Shaikh, Aswad Khadilkar, F. P. Jake Haeckl, Fausto Carnevale-Neto, Scott La, Akshar Lohith, Rachel M. Vaden, Jeon Lee, Shuguang Wei, R. Scott Lokey, Michael A. White, Roger G. Linington, John B. MacMillan
Summary: Determining the mechanism of action of natural products is a significant challenge. This study presents a comprehensive platform that integrates multiple data sources and metabolomics analysis to improve the prediction of mechanism of action and facilitate the identification of bioactive metabolites.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
Joana Santos, Maria Fernanda Proenca, Ana Joao Rodrigues, Patricia Patricio, Helena Sofia Domingues
Summary: Paroxetine is a potent inhibitor of serotonin reuptake commonly used to treat depression and neurological disorders. Research on its synthesis and derivatives has attracted interest from medicinal chemists. While progress has been made in the total synthesis of paroxetine in the past decade, there is still a need for new eco-friendly and sustainable synthetic alternatives.
CURRENT MEDICINAL CHEMISTRY
(2021)
Review
Pharmacology & Pharmacy
Olivia Pontes, Sofia Oliveira-Pinto, Fatima Baltazar, Marta Costa
Summary: Renal cell carcinoma is the most common and lethal tumor of the urological system, with various treatment options available including surgery and targeted therapies. However, the development of resistance and limited durable responses highlight the need for new anticancer candidates with improved selectivity and efficacy. Recent research has focused on novel natural and synthetic compounds for treating RCC.
DRUG DISCOVERY TODAY
(2022)
Article
Chemistry, Multidisciplinary
Alexandra Brito, Dhwanit Dave, Ayala Lampel, Vania I. B. Castro, Daniela Kroiss, Rui L. Reis, Tell Tuttle, Rein Ulijn, Ricardo A. Pires, Iva Pashkuleva
Summary: This study demonstrates that the substitution of serine with threonine affects the morphology of aggregates, while O-glycosylation decreases aggregation propensity by rebalancing pi interactions. The glycopeptides form aggregates with reduced stiffness but increased thermal stability, showing promising potential for elucidating molecular mechanisms and inspiring the design of functional glycopeptide-based biomaterials.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Ana Sofia Freitas, Marta Costa, Olivia Pontes, Veronique Seidel, Fernanda Proenca, Susana M. Cardoso, Rui Oliveira, Fatima Baltazar, Cristina Almeida-Aguiar
Summary: The study found that propolis and its constituents have potential therapeutic effects against renal cell carcinoma.
Article
Engineering, Environmental
A. C. Silva, P. Rocha, J. Antelo, P. Valderrama, R. Lopez, D. Geraldo, M. F. Proenca, J. P. Pinheiro, S. Fiol, F. Bento
Summary: The stability and maturity of organic matter are fundamental features of compost chemical characterization. Different analytical methodologies can assess the increase of chemical moieties. This study compares the ability of various methodologies to differentiate compost at different composting stages, highlighting the importance of analytical techniques in composting monitoring.
PROCESS SAFETY AND ENVIRONMENTAL PROTECTION
(2022)
Article
Chemistry, Multidisciplinary
Fabio Pedroso de Lima, Emilio Lence, Pilar Suarez de Cepeda, Carla Correia, M. Alice Carvalho, Concepcion Gonzalez-Bello, M. Fernanda Proenca
Summary: We have developed a simple and efficient method for the synthesis of highly substituted nitrogen heterocycles, which are valuable in drug discovery. Computational studies have revealed that the regioselectivity of the reaction is driven by the 2-hydroxyaryl group, leading to the formation of imidazole derivatives.
Article
Chemistry, Medicinal
Ana Sousa, Olivia Pontes, Juliana Andrade, Fatima Baltazar, Marta Costa, Fernanda Proenca
Summary: An in silico study identified a series of potentially active anti-cancer compounds, which were synthesized using a novel approach. These compounds showed inhibitory effects on renal cell carcinoma in vitro, with good selectivity towards non-neoplastic cells.
Article
Materials Science, Composites
Tania Peixoto, Joana Nunes, Maria A. Lopes, Elina Marinho, M. Fernanda Proenca, Paulo E. Lopes, Maria C. Paiva
Summary: This study reports on the preparation of few-layer graphene (FLG) and its respective PLA-based composites using an eco-friendly, efficient, and cost-effective approach. The influence of FLG on the morphology, crystallinity, thermal, and mechanical properties of the PLA composites was investigated. The composites with a loading of 0.05 wt% demonstrated suitability for potential applications where product safety is crucial.
POLYMER COMPOSITES
(2022)
Article
Pharmacology & Pharmacy
Stefania Scialla, Mahmoud S. Hanafy, Jie-Liang Wang, Nuria Genicio, Milene Costa Da Silva, Marta Costa, Sofia Oliveira-Pinto, Fatima Baltazar, Juan Gallo, Zhengrong Cui, Manuel Banobre-Lopez
Summary: A magnetic theranostic hybrid nanovehicle was developed for targeted treatment of triple-negative breast cancer (TNBC) by pH-triggered tumour associated macrophages (TAMs) targeting. The nanovehicle, composed of a Carnauba wax matrix, incorporated iron oxide nanoparticles and doxorubicin (DOX). The nanovehicles were modified with a mannose ligand and an acid-sensitive sheddable polyethylene glycol (PEG) moiety for TAMs targeting. The targeting capability towards TAMs was confirmed in vitro, and the efficacy of the targeted formulations was demonstrated in TNBC cell lines and a TNBC mouse model.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Oncology
Julieta Afonso, Celine Goncalves, Marta Costa, Debora Ferreira, Lucio Santos, Adhemar Longatto-Filho, Fatima Baltazar
Summary: Glycolysis-related proteins are associated with bladder cancer aggressiveness and poor prognosis. The HK2 inhibitor 2-deoxy-D-glucose can inhibit glycolysis, reduce bladder cancer cell invasion, and increase sensitivity to cisplatin.
Review
Biochemistry & Molecular Biology
Ana Silva, Monica Costa Cerqueira, Beatriz Rosa, Catarina Sobral, Filipa Pinto-Ribeiro, Marta Freitas Costa, Fatima Baltazar, Julieta Afonso
Summary: Cancer produces energy through accelerated glycolysis, resulting in increased lactate production. The lactate is transported to and from cancer cells by monocarboxylate transporters (MCTs). MCT1 acts as both an importer and an extruder of lactate and has been studied extensively in recent years, being generally associated with aggressive cancer. This systematic review aimed to evaluate the prognostic value of MCT1 immunoexpression in various malignancies. The results showed that MCT1 is a poor prognostic indicator and is associated with decreased survival in sixteen types of cancer. However, MCT1 overexpression was also linked to better outcomes in colorectal cancer, pancreatic ductal adenocarcinoma, and non-small cell lung cancer patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Materials Science, Biomaterials
Ana M. Martins, Alexandra Brito, Maria Grazia Barbato, Alessia Felici, Rui L. Reis, Ricardo A. Pires, Iva Pashkuleva, Paolo Decuzzi
Summary: The 3D organization of cells plays a significant role in their behavior and response to treatment. In cancer research, spheroids, organoids, and microfluidic chips are used to mimic the complex microenvironment of tumors. This study utilized microfluidic devices to replicate the spatial organization of brain tumors and evaluate the efficacy of anti-cancer agents. The results showed that brain tumor cells were more sensitive to treatment in the microfluidic device compared to traditional cell cultures. The proposed microfluidic chips can effectively reproduce the 3D structure of tumors and assess the effectiveness of therapeutic compounds.
BIOMATERIALS ADVANCES
(2023)
Article
Materials Science, Biomaterials
Natalia Vilaca, Ana Raquel Bertao, Eko Adi Prasetyanto, Sara Granja, Marta Costa, Rui Fernandes, Francisco Figueiredo, Antonio M. Fonseca, Luisa De Cola, Fatima Baltazar, Isabel C. Neves
Summary: The study demonstrates that loading anticancer drugs into zeolites can effectively inhibit the growth of breast cancer cells through endocytic mechanisms. Functionalizing the outer surface can enhance the internalization rate of drugs and lead to better tumor reduction.
MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS
(2021)
Article
Chemistry, Medicinal
Shuang Mei, Su Jiang, Yuting Wang, Han Jing, Peng Yang, Miao-Miao Niu, Jindong Li, Kai Yuan, Yan Zhang
Summary: This study identifies a dual-targeting peptide, AP-1, that effectively inhibits variants of concern (VOCs) of SARS-CoV-2 without impairing host cell viability. The findings suggest that AP-1 could be a promising broad-spectrum agent for treating emerging VOCs of SARS-CoV-2.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Hyeonjun Lee, Ju Yeon Lee, Hyunsoo Jang, Hye Young Cho, Minhee Kang, Sang Hyun Bae, Suin Kim, Eunji Kim, Jaebong Jang, Jin Young Kim, Young Ho Jeon
Summary: By using liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance experiments, we identified new chemical moieties that bind to the target sites of the protein of interest, allowing for reversible binding and protein degradation. This method has the potential to expand the application of PROTAC technology.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Yingying Li, Xiyou Du, Xinru Kong, Yuelin Fang, Zhijing He, Dongzhu Liu, Hang Wu, Jianbo Ji, Xiaoye Yang, Lei Ye, Guangxi Zhai
Summary: This study proposes a novel nanoplatform based on the autophagy cascade to overcome the obstacles in chemo-immunotherapy. The platform combines chemotherapy and starvation therapy to initiate pro-death autophagy and enhance antigen presentation, while also remodeling the immunosuppressive tumor microenvironment. Furthermore, the study discovers a new therapeutic direction for the respiration inhibitor 3-bromopyruvic acid (3BP) in cancer treatment. Overall, this study offers an opportunity to improve antitumor efficacy and boost immune responses.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Bingsi Wang, Mingxu Ma, Yusen Dai, Pengfei Yu, Liang Ye, Wenyan Wang, Chunjie Sha, Huijie Yang, Yingjie Yang, Yunjing Zhu, Lin Dong, Shujuan Wei, Linlin Wang, Jingwei Tian, Hongbo Wang
Summary: Breast cancer is a common malignant tumor in women, and drug resistance remains a clinical challenge. In this study, a novel compound, G-5b, was developed with potent antagonistic and degradation activities comparable to the current drug fulvestrant. G-5b also showed improved stability and solubility. Mechanistically, G-5b engages the proteasome pathway to degrade ER, inhibiting the ER signaling pathway and inducing apoptosis and cell cycle arrest. In animal models, G-5b exhibited superior pharmacokinetics and pharmacodynamics properties. Overall, G-5b is a promising long-acting SERD worthy of further investigation and optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Karoline B. Waitman, Larissa C. de Almeida, Marina C. Primi, Jorge A. E. G. Carlos, Claudia Ruiz, Thales Kronenberger, Stefan Laufer, Marcia Ines Goettert, Antti Poso, Sandra V. Vassiliades, Vinicius A. M. de Souza, Monica F. Z. J. Toledo, Neuza M. A. Hassimotto, Michael D. Cameron, Thomas D. Bannister, Leticia Costa-Lotufo, Joa o A. Machado-Neto, Mauricio T. Tavares, Roberto Parise-Filho
Summary: A series of hybrid inhibitors combining pharmacophores of known kinase inhibitors and benzohydroxamate HDAC inhibitors were synthesized and evaluated for their anticancer activity and pharmacokinetic properties. Compounds 4d-f exhibited promising cytotoxicity against hematological cells and moderate activity against solid tumor models. Compound 4d showed potent inhibition of multiple kinase targets and had stable interactions with HDAC and members of the JAK family. These compounds showed selective cytotoxicity with minimal effects on non-tumorigenic cells and favorable pharmacokinetic profiles.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Michal Sulik, Diana Fontinha, Dietmar Steverding, Szymon Sobczak, Michal Antoszczak, Miguel Prudencio, Adam Huczynski
Summary: This study describes the synthesis of the first-in-class ivermectin derivatives obtained through derivatization of the C13 position, along with the unexpected rearrangement of the macrolide ring. These derivatives show potential for antiparasitic activity and are important for the development of new antiparasitic agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Jun Liu, Qiu-Xian Chen, Wen-Fu Wu, Dong Wang, Si -Yu Zhao, Jia-Hao Li, Yi-Qun Chang, Shao-Gao Zeng, Jia-Yi Hu, Yu-Jie Li, Jia-Xin Du, Shu-Meng Jiao, Hai-Chuan Xiao, Qiang Zhang, Jun Xu, Jian-Fu Zhao, Hai -Bo Zhou, Yong-Heng Wang, Jian Zou, Ping-Hua Sun
Summary: A new anti-infective drug strategy has been discovered to attenuate virulence and modulate inflammation caused by drug-resistant Pseudomonas aeruginosa infections. Compound 5f inhibits biofilm formation, macrophage migration, and inflammatory response induced by P. aeruginosa, showing potential as a novel candidate against drug-resistant infections.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Liuzeng Chen, Ke Wang, Lingyun Wang, Wei Wang, Lifan Wang, Jia Li, Xiaohan Liu, Mengya Wang, Banfeng Ruan
Summary: In this study, a series of novel anti-inflammatory compounds were designed and synthesized based on the natural product pterostilbene skeleton. Among them, compound 8 showed the highest activity and exhibited its effects through inhibition of pro-inflammatory cytokines by blocking the NF-KB/MAPK signaling pathway. Compound 8 also demonstrated a good relieving effect on acute colitis in mice and showed good safety in acute toxicity experiments.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Si-Min Liang, Gui-Bin Liang, Hui-Ling Wang, Hong Jiang, Xian-Li Ma, Jian-Hua Wei, Ri-Zhen Huang, Ye Zhang
Summary: A series of novel multi-target antitumor agents were designed, synthesized, and evaluated. Some compounds exhibited significant antitumor activity and one compound showed excellent efficacy, limited toxicity, and low resistance. Further mechanism studies revealed that the compound exerted antitumor effects through multiple pathways.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
