Review
Biochemistry & Molecular Biology
Mudasir Nabi Peerzada, Aysha Gaur, Amir Azam
Summary: This review discusses drug development strategies for human African and American trypanosomiasis, highlighting the most promising compounds identified through various approaches and emphasizing the potential of molecular hybridization in preventing the development of resistance.
CURRENT MEDICINAL CHEMISTRY
(2021)
Article
Medicine, Research & Experimental
Desiree San Nicolas-Hernandez, Eduardo Hernandez-Alvarez, Carlos J. Bethencourt-Estrella, Atteneri Lopez-Arencibia, Ines Sifaoui, Isabel L. Bazzocchi, Jacob Lorenzo-Morales, Ignacio A. Jimenez, Jose E. Pinero
Summary: This study reports the synthesis, screening, and mechanism study of fourteen withaferin A derivatives. Nine of them showed potent inhibitory effects on the proliferation of Leishmania and Trypanosoma cruzi parasites, with one derivative being the most effective. These results highlight the potential of withaferin A-related steroids in treating neglected tropical diseases caused by Leishmania and T. cruzi parasites.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Immunology
Aline Maria Vasconcelos Queiroz, Johny Wysllas de Freitas Oliveira, Claudia Jassica Moreno, Diego M. A. Guerin, Marcelo Sousa Silva
Summary: Current research focuses on using VLP technology to develop vaccines against trypanosomatids, a family of protozoa causing neglected tropical diseases. This approach offers potential to combat diseases such as Chagas disease, leishmaniasis, and sleeping sickness, by targeting protozoan antigens.
Review
Microbiology
Natalia Tiberti, Silvia Stefania Longoni, Valery Combes, Chiara Piubelli
Summary: Blood and tissue protozoan infections pose a significant burden in tropical and subtropical regions, with potential impacts even in high-income countries due to migration and travel. The lack of proper therapeutic interventions and effective vaccine strategies remains a challenge in controlling these diseases, while the pathophysiological mechanisms behind them are still not fully understood. Extracellular vesicles (EVs) have garnered interest for their role in modulating interactions between parasites and hosts, offering potential insights for disease mechanisms and diagnostic markers.
Review
Pharmacology & Pharmacy
Leonardo L. G. Ferreira, Josue de Moraes, Adriano D. Andricopulo
Summary: Neglected tropical diseases, such as leishmaniasis and schistosomiasis, continue to be a public health challenge in developing countries. However, advancements in drug discovery using modern strategies have shown promise in addressing these diseases by combining medicinal chemistry and parasite biology.
DRUG DISCOVERY TODAY
(2022)
Review
Veterinary Sciences
Keneth Iceland Kasozi, Ewan Thomas MacLeod, Ibrahim Ntulume, Susan Christina Welburn
Summary: African trypanosomiasis, both in animals and humans, is associated with different pathogens and drug resistance. Research is being conducted on new combination therapies.
FRONTIERS IN VETERINARY SCIENCE
(2022)
Review
Chemistry, Medicinal
Igor Jose dos Santos Nascimento, Thiago Mendonca de Aquino, Edeildo Ferreira da Silva-Junior
Summary: This review discusses the development of cruzain and rhodesain inhibitors in the past 10 years, which could serve as a basis for the discovery of new trypanocidal drugs in the future.118 studies on inhibitors of cruzain and rhodesain were identified, indicating the potential for developing new treatments against Chagas disease and sleeping sickness.
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2021)
Article
Infectious Diseases
Gerardo J. Pacheco, Lawrence Fulton, Jose Betancourt, Ram Shanmugam, Paula Stigler Granados
Summary: This study uses geospatial and sensitivity analysis to better allocate resources and educational information for Chagas Disease (CD) in Texas, a neglected zoonotic disease in the Americas. The study reveals that CD cases are primarily concentrated in urban areas with increased access to healthcare resources and diagnostic capabilities.
BMC INFECTIOUS DISEASES
(2022)
Article
Chemistry, Medicinal
Valeria Napolitano, Piotr Mroz, Monika Marciniak, Vishal C. Kalel, Charlotte A. Softley, Julian D. Janna Olmos, Bettina G. Tippler, Kenji Schorpp, Sarah Rioton, Tony Froehlich, Oliver Plettenburg, Kamyar Hadian, Ralf Erdmann, Michael Sattler, Grzegorz M. Popowicz, Maciej Dawidowski, Grzegorz Dubin
Summary: Trypanosomiases are neglected tropical diseases caused by Trypanosoma (sub)species. The inhibition of the PEX5-PEX14 protein-protein interaction has shown potential as a lethal treatment for Trypanosoma. Researchers have developed a novel compound scaffold that inhibits PEX5-PEX14 PPI and has demonstrated trypanocidal activity in cell-based assays.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Juliane S. Lanza, Virginia M. R. Vallejos, Guilherme S. Ramos, Ana Carolina B. de Oliveira, Cynthia Demicheli, Luis Rivas, Sebastien Pomel, Philippe M. Loiseau, Frederic Frezard
Summary: This study evaluates the effectiveness of nanoassemblies made from antimony(V) complexes with octanoyl-N-methylglucamide (SbL8) or decanoyl-N-methylglucamide (SbL10) in targeting infection sites in visceral and cutaneous leishmaniases. The results show that these nanoassemblies are stable at neutral pH and effectively accumulate in macrophages and the liver. SbL10 exhibits higher activity against intramacrophage Leishmania amastigotes and can be further enhanced with co-incorporated miltefosine. In vivo, NanoSb demonstrates high antileishmanial activity in murine models of VL and CL. This study supports the potential of NanoSb as a better delivery system for antimony and co-incorporated drugs compared to conventional antimonial Glucantime (R).
Article
Chemistry, Medicinal
Michael G. Thomas, Kate McGonagle, Paul Rowland, David A. Robinson, Peter G. Dodd, Isabel Camino-Diaz, Lorna Campbell, Juan Cantizani, Pablo Castaneda, Daniel Conn, Peter D. Craggs, Darren Edwards, Liam Ferguson, Andrew Fosberry, Laura Frame, Panchali Goswami, Xiao Hu, Justyna Korczynska, Lorna MacLean, Julio Martin, Nicole Mutter, Maria Osuna-Cabello, Christy Paterson, Imanol Pena, Erika G. Pinto, Caterina Pont, Jennifer Riley, Yoko Shishikura, Frederick R. C. Simeons, Laste Stojanovski, John Thomas, Karolina Wrobel, Robert J. Young, Filip Zmuda, Fabio Zuccotto, Kevin D. Read, Ian H. Gilbert, Maria Marco, Timothy J. Miles, Pilar Manzano, Manu De Rycker
Summary: There is an urgent need for new treatments for Chagas disease. The discovery of a preclinical candidate for visceral leishmaniasis prompted the investigation of alternative proteasome inhibitors for Trypanosoma cruzi, the parasite causing Chagas disease. A selective pyridazinone compound was identified and optimized for efficacy studies, showing potential as a new treatment for Chagas disease.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Parasitology
H. A. Walters, L. A. Temesvari
Summary: Protozoan parasites are single-celled eukaryotic organisms that cause significant human disease and pose a substantial health and socioeconomic burden worldwide. Transcription factors, which were previously thought to be undruggable, are now considered appealing drug targets for anti-parasitic drug design. Understanding parasite transcriptional pathways and how parasites alter host gene expression will be essential in discovering innovative drug targets.
INTERNATIONAL JOURNAL FOR PARASITOLOGY
(2021)
Article
Chemistry, Medicinal
Ina Poehner, Antonio Quotadamo, Joanna Panecka-Hofman, Rosaria Luciani, Matteo Santucci, Pasquale Linciano, Giacomo Landi, Flavio Di Pisa, Lucia Dello Iacono, Cecilia Pozzi, Stefano Mangani, Sheraz Gul, Gesa Witt, Bernhard Ellinger, Maria Kuzikov, Nuno Santarem, Anabela Cordeiro-da-Silva, Maria P. Costi, Alberto Venturelli, Rebecca C. Wade
Summary: In this study, a systematic and multidisciplinary approach was used to develop selective antiparasitic compounds. Through computational fragment-based design and crystallographic structure determination, compounds with activity against multiple targets were obtained. Additionally, the combination of polypharmacology design and parasite-specific optimization led to the discovery of compounds effective against T. brucei brucei.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Veterinary Sciences
Keneth Iceland Kasozi, Ewan Thomas MacLeod, Susan Christina Welburn
Summary: The resistance of African animal trypanocide is a continuous threat to the elimination of African trypanosomiasis. This study investigated the threat by using major chemotherapeutic agents and found multi-drug cross-resistance, emphasizing the need to revise policies for disease control.
FRONTIERS IN VETERINARY SCIENCE
(2023)
Review
Pharmacology & Pharmacy
Maribel Navarro, Rodrigo M. S. Justo, Giset Y. Sanchez Delgado, Gonzalo Visbal
Summary: The evaluation of late transition metal complexes for the treatment of Trypanosomatid diseases and some insights about their mechanism of action are provided.
CURRENT PHARMACEUTICAL DESIGN
(2021)
Article
Behavioral Sciences
Carol Paronis, Christos Iliopoulos-Tsoutsouvas, Ioannis Papanastasiou, Alex Makriyannis, Jack Bergman, Spyros P. Nikas
Summary: This study aimed to evaluate the spontaneous withdrawal response in mice following exposure to cannabinoids. The results showed that mice exhibited behavioral changes including tremors and decreased body temperature after cannabinoid exposure. Additionally, the degree of cannabinoid dependence may vary in relation to the dose and efficacy of the drug.
BEHAVIOURAL PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Ioannis P. Papanastasiou, Markos-Orestis Georgiadis, Christos Iliopoulos-Tsoutsouvas, Carol A. Paronis, Christina A. Brust, Ngan K. Tran, Lipin Ji, Xiaoyu Ma, JodiAnne T. Wood, Nikolai Zvonok, Fei Tong, Laura M. Bohn, Spyros P. Nikas, Alexandros Makriyannis
Summary: This study merged the features of nabilone and AM2389 and optimized the C3 side chain. Among the nabilone analogs, AM8936 exhibited balanced and potent agonist activity on the CB1 receptor, making it a potential candidate for further development.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Nikitas Georgiou, Niki Gouleni, Eleni Chontzopoulou, George S. Skoufas, Anastasios Gkionis, Demeter Tzeli, Stamatia Vassiliou, Thomas Mavromoustakos
Summary: In this study, the structure assignment and conformational analysis of cinnamic derivative N-benzyl-N-(2-(cyclohexylamino)-2-oxoethyl) cinnamamide (NGI25) were conducted using various techniques such as Nuclear Magnetic Resonance spectroscopy, Molecular Dynamics, and Quantum Mechanics calculations. The results indicate that NGI25 adopts similar conformations in different solvents and exhibits potential inhibitory effects on butyrylcholinesterase and lipoxygenase enzymes.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Marilena Vlachou, Angeliki-Sofia Foscolos, Angeliki Siamidi, Angeliki Syriopoulou, Nikitas Georgiou, Aikaterini Dedeloudi, Antonis D. Tsiailanis, Andreas G. Tzakos, Thomas Mavromoustakos, Ioannis P. Papanastasiou
Summary: The aqueous dissolution profiles and structural characteristics of isomeric synthetic adamantane phenylalkylamine hydrochlorides I and II were studied. These compounds exhibit significant antiproliferative/anticancer activity and analgesic properties against neuropathic pain, while being non-toxic. The structures of the compounds were elucidated using 2D NMR experiments and confirmed by molecular dynamics simulations.
Article
Chemistry, Medicinal
Andrew Tsotinis, Pandelis A. Afroudakis, Ioannis P. Papanastasiou, Aikaterini Sakellaropoulou, Marina Boniakou, Dimitri Komiotis, Peter J. Garratt, Philippe Delagrange, Alina Bocianowska-Zbrog, David Sugden
Summary: A series of substituted indolo[2,1-a]isoquinolines and indolo[1,2-a]benzoxazines have been prepared as melatonin analogues and their agonist and antagonist potency, as well as binding affinity, have been investigated. Certain compounds exhibit strong binding affinity and preference for the hMT2 receptor, while weak binding affinity for the hMT1 receptor.
Article
Biochemistry & Molecular Biology
John M. Matsoukas, Laura Kate Gadanec, Anthony Zulli, Vasso Apostolopoulos, Konstantinos Kelaidonis, Irene Ligielli, Kalliopi Moschovou, Nikitas Georgiou, Panagiotis Plotas, Christos T. Chasapis, Graham Moore, Harry Ridgway, Thomas Mavromoustakos
Summary: Diminazene aceturate (DIZE) is a potential angiotensin-converting enzyme 2 (ACE2) activator and angiotensin type 1 receptor antagonist (AT(1)R). It converts toxic angiotensin II (AngII) to vasodilatory peptides and shows promise as a treatment for COVID-19.
Article
Biochemistry & Molecular Biology
Cisem Altunayar-Unsalan, Ozan Unsalan, Thomas Mavromoustakos
Summary: The study indicates that hesperidin can increase the fluidity and thickness of model membranes, playing an important role in simulating mammalian membranes. Furthermore, hesperidin may serve as a potential therapeutic agent for hypercholesterolemia due to its antioxidant properties.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Virology
Harry Ridgway, Charalampos Ntallis, Christos T. T. Chasapis, Konstantinos Kelaidonis, Minos-Timotheos Matsoukas, Panagiotis Plotas, Vasso Apostolopoulos, Graham Moore, Sotirios Tsiodras, Dimitrios Paraskevis, Thomas Mavromoustakos, John M. M. Matsoukas
Summary: This study reported the variant distribution of SARS-CoV-2 across EU/EEA countries and investigated the driving forces behind mutations that trigger infections. Computational approaches were used to examine the stabilizing effects of key mutations on the RBD-ACE2 complex in Alpha, Beta, Gamma, Delta, Epsilon, Kappa, Lambda, and Omicron variants. Critical mutations found in the delta variant and two omicron variants were identified, which may contribute to increased transmissibility and morbidity.
Article
Chemistry, Medicinal
Marianna Stampolaki, Satish R. Malwal, Nadine Alvarez-Cabrera, Zijun Gao, Mohammad Moniruzzaman, Svitlana O. Babii, Nikolaos Naziris, Andre Rey-Cibati, Mariana Valladares-Delgado, Andreea L. Turcu, Kyung-Hwa Baek, Phan Trong-Nhat, Hyeryon Lee, Mattheo Alcaraz, Savannah Watson, Mariette van der Watt, Dina Coertzen, Natasa Efstathiou, Maria Chountoulesi, Carolyn M. Shoen, Ioannis P. Papanastasiou, Jose Brea, Michael H. Cynamon, Lyn-Marie Birkholtz, Laurent Kremer, Joo Hwan No, Santiago Vazquez, Gustavo Benaim, Costas Demetzos, Helen I. Zgurskaya, Thomas Dick, Eric Oldfield, Antonios D. Kolocouris
Summary: SQ109 is a potent tuberculosis drug candidate that inhibits MmpL3 transporter and cell wall biosynthesis in Mycobacterium tuberculosis. It also shows activity against bacteria and protozoan parasites. In this study, 18 analogs of SQ109 were synthesized and tested against various microorganisms. Some analogs showed more activity than SQ109 against drug-resistant M. abscessus and P. falciparum. These analogs also exhibited low toxicity to human cells, making them potential antimalarial drug leads. Surface plasmon resonance and differential scanning calorimetry were used to study the binding of inhibitors to MmpL3 and lipid membranes, respectively.
ACS INFECTIOUS DISEASES
(2023)
Article
Biochemistry & Molecular Biology
Angeliki Chroni, Thomas Mavromoustakos, Stergios Pispas
Summary: The current study focused on developing innovative and highly-stable curcumin-based therapeutics by encapsulating curcumin in biocompatible poly(n-butyl acrylate)-block-poly(oligo(ethylene glycol) methyl ether acrylate) micelles. The successful encapsulation of curcumin within the micelles was confirmed by various techniques, and the exceptional stability of the curcumin-loaded nanocarriers was demonstrated. The research provides new understanding of the encapsulation and release mechanisms of curcumin within biocompatible diblock copolymers and has significant implications for the advancement of safe and effective curcumin-based therapeutics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Konstantinos Kelaidonis, Irene Ligielli, Spiros Letsios, Veroniki P. P. Vidali, Thomas Mavromoustakos, Niki Vassilaki, Graham J. J. Moore, Weronika Hoffmann, Katarzyna Wegrzyn, Harry Ridgway, Christos T. T. Chasapis, John M. M. Matsoukas
Summary: This study investigated the role of tetrazole in binding and the network of amino acids of SARS-CoV-2 Spike RBD-ACE2 complex involved in interactions with sartans. The study found that bisartans, a novel class of synthetic antihypertensive drugs, show stronger docking to ACE2 compared to commercially available hypertension drugs. It was also revealed that tetrazole plays a critical role in the binding of sartans and bisartans to the ACE2/Spike complex.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Nikitas Georgiou, Eleni Chontzopoulou, Antigoni Cheilari, Aikaterini Katsogiannou, Danai Karta, Kyriaki Vavougyiou, Dimitra Hadjipavlou-Litina, Uros Javornik, Janez Plavec, Demeter Tzeli, Stamatia Vassiliou, Thomas Mavromoustakos
Summary: The potential of compounds KKII5 and DKI5 as drug leads is investigated. The structure, binding in the active site of the LOX-1 enzyme, and toxicity of KKII5 and DKI5 are studied via experimental and computational methodologies. The results show that both compounds have favorable binding in the active site and exhibit potential as drug leads.
Article
Biochemistry & Molecular Biology
Despoina P. P. Kiouri, Charalampos Ntallis, Konstantinos Kelaidonis, Massimiliano Peana, Sotirios Tsiodras, Thomas Mavromoustakos, Alessandro Giuliani, Harry Ridgway, Graham J. J. Moore, John M. M. Matsoukas, Christos T. T. Chasapis
Summary: The potential of targeting the RAAS as a treatment for COVID-19 is being investigated. This study analyzed the potential side effects and off-target effects of antihypertensive drugs, ARBs, and Pfizer's antiviral drug, Paxlovid, for COVID-19 treatment. The findings compared the effects and possible risks of both drug categories.
Article
Biochemistry & Molecular Biology
Kalliopi Moschovou, Maria Antoniou, Eleni Chontzopoulou, Konstantinos D. Papavasileiou, Georgia Melagraki, Antreas Afantitis, Thomas Mavromoustakos
Summary: In this in silico study, the potential of natural products and antihypertensive molecules as inhibitors targeting key proteins of the SARS-CoV-2 virus was explored. Docking and molecular dynamics simulations revealed the binding affinities and stability of protein-ligand complexes. The study identified potential drug candidates and multi-target inhibitors for disrupting the SARS-CoV-2 virus lifecycle.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Marianna Stampolaki, Satish R. Malwal, Nadine Alvarez-Cabrera, Zijun Gao, Mohammad Moniruzzaman, Svitlana O. Babii, Nikolaos Naziris, Andre Rey-Cibati, Mariana Valladares-Delgado, Andreea L. Turcu, Kyung-Hwa Baek, Trong-Nhat Phan, Hyeryon Lee, Mattheo Alcaraz, Savannah Watson, Mariette van der Watt, Dina Coertzen, Natasa Efstathiou, Maria Chountoulesi, Carolyn M. Shoen, Ioannis P. Papanastasiou, Jose Brea, Michael H. Cynamon, Lyn-Marie Birkholtz, Laurent Kremer, Joo Hwan No, Santiago Vazquez, Gustavo Benaim, Costas Demetzos, Helen I. Zgurskaya, Thomas Dick, Eric Oldfield, Antonios D. Kolocouris
Summary: SQ109 is a potent tuberculosis drug candidate that targets cell wall biosynthesis by inhibiting MmpL3 transporter. It also shows activity against bacteria and protozoan parasites. By synthesizing analogs of SQ109, higher activity against drug-resistant strains of Mycobacterium abscessus and Plasmodium falciparum was found, making them potential new drug leads. Binding studies suggest that MmpL3 is not a major target in mycobacteria. Rating: 7/10.
ACS INFECTIOUS DISEASES
(2023)
