Review
Biochemistry & Molecular Biology
Wenjing Liu, Min He, Yongjun Li, Zhiyun Peng, Guangcheng Wang
Summary: Chalcone derivatives have been found to disrupt the dynamic balance of microtubules, inhibit tumor cell proliferation, and exhibit anti-tumor effects. By inhibiting microtubule dynamics and disrupting microtubule homeostasis, they interfere with the process of cell mitosis.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Celina de Jesus Guimaraes, Teiliane Rodrigues Carneiro, Marisa Jadna Silva Frederico, Guilherme G. C. de Carvalho, Matthew Little, Valder N. Freire, Victor L. B. Franca, Daniel Nascimento do Amaral, Jessica de Siqueira Guedes, Eliezer J. Barreiro, Lidia Moreira Lima, Francisco W. A. Barros-Nepomuceno, Claudia Pessoa
Summary: LASSBio-1920 was synthesized to overcome the poor solubility of its natural precursor, CA4. The compound exhibited cytotoxic potential against human colorectal cancer cells and non-small cell lung cancer cells. It induced apoptosis and had enzyme-substrate interactions similar to other tyrosine kinase inhibitors. LASSBio-1920 showed good absorption and high CNS permeability, and accumulated in various organs. The obtained pharmacokinetic parameters will guide further in vivo studies on its antitumor potential.
Article
Biochemistry & Molecular Biology
Edua Kovacs, Hazhmat Ali, Renata Minorics, Peter Traj, Vivien Resch, Gabor Paragi, Bella Bruszel, Istvan Zupko, Erzsebet Mernyak
Summary: Novel 13 alpha-estrone derivatives were synthesized through direct arylation of the phenolic hydroxy function. The antiproliferative activities of the synthesized compounds against human cancer cell lines were investigated, and the quinoline derivative showed substantial activity with low IC50 values. Disturbance of tubulin polymerization was confirmed, and computational calculations revealed significant interactions of the quinoline derivative with the taxoid binding site of tubulin.
Article
Chemistry, Medicinal
Abdelfattah Faouzi, Alexandre Arnaud, Alexandre Bancet, Caroline Barette, Jordane Preto, Cong Viet Do, Lars Petter Jordheim, Zineb Bousfiha, Thi Thanh Binh Nguyen, Marion Verriere, Amaury Farce, Marie-Odile Fauvarque, Roland Barret, Thierry Lomberget
Summary: Novel heterocyclic derivatives inspired by Combretastatin A-4 were synthesized and evaluated for their biological activities on tubulin polymerization and cell proliferation. Compounds (Z)-4h and (Z)-4j exhibited significant in cellulo tubulin polymerization inhibition and antiproliferative activities. Molecular docking studies were conducted to understand the interactions with the protein target, and apoptotic processes were observed in follicular lymphoma cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Anuradha Kumari, Shweta S. Prassanawar, Dulal Panda
Summary: Indibulin, a microtubule-depolymerizing agent, shows minimal neurotoxicity and is less cytotoxic towards differentiated neuronal cells. It binds to beta-tubulin isotypes differently and has a lower affinity to beta-III tubulin. Depletion of beta-III tubulin increases the toxicity of indibulin and colchicine, while vinblastine is unaffected. Indibulin inhibits colchicine binding to tubulin and is a colchicine-site binder.
ACS CHEMICAL NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Maria Cecilia Gonzalez Garcia, Caroline Radix, Claude Villard, Gilles Breuzard, Pascal Mansuelle, Pascale Barbier, Philipp O. Tsvetkov, Harold De Pomyers, Didier Gigmes, Francois Devred, Herve Kovacic, Kamel Mabrouk, Jose Luis
Summary: In this study, we identified myotoxin-3, a peptide from the venom of the Northern Pacific rattlesnake, as a potential microtubule targeting agent. Myotoxin-3 increased tubulin polymerization and showed slight toxicity against glioblastoma and breast carcinoma cells. It also induced remodeling of the microtubule network and decreased microtubule dynamic instability. These effects were attributed to the direct interaction of myotoxin-3 with tubulin. Our findings suggest that exogenous peptides, such as myotoxin-3, could be promising candidates for the development of new anti-cancer drugs, and venom is a valuable source of pharmacologically active molecules.
Article
Immunology
Samvel Sirakanyan, Erik Arabyan, Astghik Hakobyan, Tamara Hakobyan, Garri Chilingaryan, Harutyun Sahakyan, Arsen Sargsyan, Grigor Arakelov, Karen Nazaryan, Roza Izmailyan, Liana Abroyan, Zaven Karalyan, Elina Arakelova, Elmira Hakobyan, Anush Hovakimyan, Andre Serobian, Marco Neves, Joao Ferreira, Fernando Ferreira, Hovakim Zakaryan
Summary: This study identified three new compounds with anti-ASFV activity by targeting the colchicine binding site of tubulin. The most promising compound, 6b, showed dose-dependent reduction of ASFV replication with no cellular or animal toxicity. Compound 6b interfered with ASFV attachment, internalization, and egress, and had higher antiviral effects when added within 2-8 h post-infection. Additionally, compound 6b promoted tubulin polymerization, acting as a microtubule-stabilizing agent.
EMERGING MICROBES & INFECTIONS
(2021)
Article
Chemistry, Medicinal
Wolfgang Dohle, Hannah Asiki, Wojciech Gruchot, Paul A. Foster, Havreen K. Sahota, Ruoli Bai, Kirsten E. Christensen, Ernest Hamel, Barry V. L. Potter
Summary: 2-Difluoromethoxyestratriene derivatives were designed to improve the potency and stability of the drug candidate 2-methoxyestradiol (2ME2). Evaluation showed that these compounds exhibit promising anti-cancer activity and significant inhibition of steroid sulfatase and tubulin.
Article
Chemistry, Medicinal
Azizah M. Malebari, Gabriela Duffy Morales, Brendan Twamley, Darren Fayne, Mohemmed Faraz Khan, Eavan C. McLoughlin, Niamh M. O'Boyle, Daniela M. Zisterer, Mary J. Meegan
Summary: This study describes the synthesis, characterization, and mechanism of action of a series of 3-fluoro and 3,3-difluoro substituted beta-lactams as analogues of the tubulin-targeting agent CA-4. These compounds showed potent activity in breast cancer cells and low toxicity in non-cancerous cells. Mechanistic studies demonstrated that these compounds inhibit tubulin polymerization and induce apoptosis, making them potential candidates for the development of novel cancer therapeutics.
Article
Multidisciplinary Sciences
Godshelp O. Egharevba, Ahmed Kamal, Omotayo O. Dosumu, Sunitha Routhu, Olatomide A. Fadare, Stephen O. Oguntoye, Stanislaus N. Njinga, Abimbola P. Oluyori
Summary: The novel 1,1-diaryl vinyl-sulfones analogues were synthesized and screened for their antiproliferative activity against various cancer cell lines. The compounds showed better cytotoxicity against certain cancer cell lines and had no toxicity towards normal cells. Compounds with higher cell permeability demonstrated optimal cytotoxicity, highlighting the importance of cell permeability in enhancing the cytotoxicity of these compounds.
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Medicinal
Azizah M. Malebari, Shu Wang, Thomas F. Greene, Niamh M. O'Boyle, Darren Fayne, Mohemmed Faraz Khan, Seema M. Nathwani, Brendan Twamley, Thomas McCabe, Daniela M. Zisterer, Mary J. Meegan
Summary: The novel 3-chloro-2-azetidinones show potent antiproliferative effects in breast cancer cells and exhibit similar cellular effects as Combretastatin A-4. The compounds act by inhibiting tubulin polymerization and inducing late-phase cell cycle arrest.
Article
Biochemistry & Molecular Biology
Masayo Hirao-Suzuki, Koki Kanameda, Masufumi Takiguchi, Narumi Sugihara, Shuso Takeda
Summary: This study examined the efficacy of microtubule-destabilizing agents G-1 and 2-MeO-E2 in treating endocrine therapy-resistant breast cancer cells. The results showed that 2-MeO-E2 selectively inhibited the proliferation of LTED cells, which was associated with the high expression of beta-tubulin proteins and TUBB2B in LTED cells.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Farhat Firdous, Rida Ibrahim, Muhammad Furqan, Hina Khan, Hadeeqa Raza, Upendra Singh, Abdul-Hamid Emwas, Mariusz Jaremko, Ghayoor Abbas Chotana, Amir Faisal, Rahman Shah Zaib Saleem
Summary: Griseofulvin derivatives showed activity in breast cancer cells, with the most promising compound characterized as a microtubule-stabilizing agent and also inhibiting proliferation of other cancer cells.
Article
Chemistry, Multidisciplinary
Fatma Elzahraa Ali, Ola I. A. Salem, Mohamed A. El-Mokhtar, Ahmed S. Aboraia, Samia G. Abdel-Moty, Abu-Baker M. Abdel-Aal
Summary: Malignant transformations rely on increased tubulin and microtubule activities for various cancer cell processes. In this study, lipidated 1,3-diaryl propenones and their cyclized pyrimidine derivatives were designed and synthesized as tubulin polymerization inhibitors. The derivatives exhibited lipophilicity, ease of synthesis, and antiproliferative activity. The most potent derivative, compound 19, displayed significant antiproliferative activity in breast and liver cancer cell lines. Compound 19 induced cell cycle arrest and apoptosis, targeting the tubulin protein.
RESULTS IN CHEMISTRY
(2023)
Review
Oncology
Neha Devi, Kamalpreet Kaur, Avadh Biharee, Vikas Jaitak
Summary: Indole derivatives as anti-cancer agents have multiple mechanisms of action and show promising anti-cancer potential, including inducing apoptosis, inhibiting estrogen receptor, and inhibiting tyrosine kinase. Studies have shown that indole derivatives exhibit significant activity against cancer cell lines.
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Shubhangi Kandwal, Darren Fayne
Summary: The COVID-19 pandemic has had a negative impact on global human life, causing economic crises and health emergencies. In this study, computational drug design technologies were used to repurpose existing drugs as inhibitors of SARS-CoV-2 viral proteins. The results may help accelerate drug development against COVID-19 and have significant implications.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Chemistry, Medicinal
Gloria Ana, Patrick M. Kelly, Azizah M. Malebari, Sara Noorani, Seema M. Nathwani, Brendan Twamley, Darren Fayne, Niamh M. O'Boyle, Daniela M. Zisterer, Elisangela Flavia Pimentel, Denise Coutinho Endringer, Mary J. Meegan
Summary: The synthesis and biochemical evaluation of novel compounds designed as hybrids of microtubule targeting benzophenone phenstatin and aromatase inhibitor letrozole were reported. One compound showed potent antiproliferative effects in breast cancer cells, inducing G(2)/M phase cell cycle arrest and apoptosis, and selectively targeting cancer cells while sparing non-tumorigenic cells. These compounds hold promise as potential agents for breast cancer treatment.
Article
Biochemistry & Molecular Biology
Christina Cahill, Fiona O'Connell, Karl M. Gogan, Donal J. Cox, Sharee A. Basdeo, Jacintha O'Sullivan, Stephen V. Gordon, Joseph Keane, James J. Phelan
Summary: The study found that the iron chelator desferrioxamine, used as an adjunctive treatment to bedaquiline, significantly reduced the bacterial load in human macrophages infected with BCG. Additionally, it increased specific cytokine levels, indicating a potential link between enhanced bactericidal activity and cytokine production with the addition of desferrioxamine.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Noor Essa, Fiona O'Connell, Adriele Prina-Mello, Jacintha O'Sullivan, Simone Marcone
Summary: The relationship between obesity and cancer has been well characterized, but the biological mechanisms in obese cancer patients are still unclear. The obese tumor microenvironment provides additional benefits to tumor cells against anticancer therapies by altering the extracellular matrix composition and immune cell profile, while nanotechnology, particularly gold nanoparticles, is being researched for cancer treatment due to their sensitizing abilities for cancer cells and enhancement of drug delivery.
Article
Medicine, Research & Experimental
Rebecca Amet, Viola Previtali, Helene B. Mihigo, Emily Sheridan, Sarah Brophy, Nadhim Kamil Hante, Maria Jose Santos-Martinez, Patrick J. Hayden, Paul Browne, Isabel Rozas, Anthony M. McElligott, Daniela M. Zisterer
Summary: VP79s is a novel guanidinium-based compound that exhibits cytotoxicity in multiple myeloma cells. It inhibits the IL-6/STAT3 signaling pathway and downregulates MCL-1 expression, resulting in selective anti-tumor activity.
Article
Oncology
Eimear Mylod, Fiona O'Connell, Noel E. Donlon, Christine Butler, John V. Reynolds, Joanne Lysaght, Melissa J. Conroy
Summary: Esophagogastric adenocarcinomas (OAC) are obesity-associated malignancies with severe immune dysregulation. Previously, it has been shown that natural killer (NK) cells migrate preferentially to OAC omentum, where they undergo phenotypic and functional alterations and apoptosis. The CX3CR1:fractalkine (CX3CL1) pathway has been identified as pivotal in their recruitment to the omentum. This study investigates the impact of exposure to the soluble microenvironment of OAC omentum, particularly fractalkine and IL-15, on NK cell homing capacity towards esophageal tumors. The results reveal that exposure to omental adipose tissue conditioned media (ACM) diminishes NK cell migration towards OAC tumor tissue conditioned media (TCM), but this migration can be rescued with the CX3CR1 antagonist E6130. Furthermore, it is shown that fractalkine has opposing effects on NK cell migration towards TCM, whether used alone or in combination with IL-15, and inhibits IL-15-mediated stimulation of death receptor ligand expression. Interestingly, treatment with fractalkine and/or IL-15 does not significantly affect NK cell adhesion to MAdCAM-1, despite changes in integrin alpha 4 beta 7 expression. This study provides additional evidence for the therapeutic potential of CX3CR1 antagonism in rescuing NK cells from the adverse effects of the omentum and fractalkine, thereby limiting their dysfunction.
Article
Chemistry, Medicinal
Azizah M. Malebari, Shu Wang, Thomas F. Greene, Niamh M. O'Boyle, Darren Fayne, Mohemmed Faraz Khan, Seema M. Nathwani, Brendan Twamley, Thomas McCabe, Daniela M. Zisterer, Mary J. Meegan
Summary: The novel 3-chloro-2-azetidinones show potent antiproliferative effects in breast cancer cells and exhibit similar cellular effects as Combretastatin A-4. The compounds act by inhibiting tubulin polymerization and inducing late-phase cell cycle arrest.
Article
Chemistry, Medicinal
Giuseppe Campiani, Tuhina Khan, Cristina Ulivieri, Leopoldo Staiano, Chiara Papulino, Stefania Magnano, Seema Nathwani, Anna Ramunno, Daniel Lucena-Agell, Nicola Relitti, Stefano Federico, Luca Pozzetti, Gabriele Carullo, Alice Casagni, Simone Brogi, Francesca Vanni, Paola Galatello, Magda Ghanim, Niamh McCabe, Stefania Lamponi, Massimo Valoti, Ola Ibrahim, Jeffrey O'Sullivan, Richard Turkington, Vincent P. Kelly, Ruben VanWemmel, J. Fernando Diaz, Sandra Gemma, Daniela Zisterer, Lucia Altucci, Antonella De Matteis, Stefania Butini, Rosaria Benedetti
Summary: Autophagy, a crucial mechanism for maintaining organismal homeostasis, has become a focus in cancer therapy. In this study, new multifunctional agents with both pro-apoptotic and autophagy-inhibiting effects were designed and their therapeutic potential was demonstrated through experiments.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Maria Davern, Marie-Claire Fitzgerald, Croi E. Buckley, Aisling B. Heeran, Noel E. Donlon, Jason McGrath, Fiona O' Connell, Malvika R. Deshpande, Conall Hayes, Jamie MacDonald, Andrew D. Sheppard, John Reynolds, Stephen G. Maher, Niamh Lynam-Lennon, Brona Murphy, Joanne Lysaght
Summary: Recent studies have shown that immune checkpoint receptors are expressed on OAC cells and may provide a survival advantage. PD-1 and TIGIT signaling in OAC cells play a role in either promoting or inhibiting cell survival, especially under conditions of nutrient-deprivation and hypoxia. The study found that glucose-deprivation and hypoxia can upregulate PD-1 and TIGIT expression on OAC cells, and blocking PD-1 or TIGIT can have different effects on cell proliferation and survival under different conditions.
TRANSLATIONAL ONCOLOGY
(2022)
Article
Oncology
Niamh H. McCabe, Leanne Stevenson, Enya Scanlon, Rosalie Douglas, Susanna Kennedy, Oliver Keminer, Bjoern Windshuegel, Daniela Zisterer, Richard D. Kennedy, Jaine K. Blayney, Richard C. Turkington
Summary: Oesophageal adenocarcinoma (OAC), a common cancer with poor prognosis, is often resistant to chemotherapy. This study identified targeting Src as a potential strategy to enhance the efficacy of chemotherapy in OAC cells, providing new insights for developing therapeutic approaches.
Article
Biochemical Research Methods
Jessica Braun, Darren Fayne
Summary: A method using the K-means clustering algorithm to derive pharmacophore models of the binding site from fragment flooded X-ray protein structures was developed and validated by comparing with X-ray ligand structure-derived pharmacophores.
JOURNAL OF MOLECULAR GRAPHICS & MODELLING
(2022)
Article
Chemistry, Medicinal
Azizah M. Malebari, Gabriela Duffy Morales, Brendan Twamley, Darren Fayne, Mohemmed Faraz Khan, Eavan C. McLoughlin, Niamh M. O'Boyle, Daniela M. Zisterer, Mary J. Meegan
Summary: This study describes the synthesis, characterization, and mechanism of action of a series of 3-fluoro and 3,3-difluoro substituted beta-lactams as analogues of the tubulin-targeting agent CA-4. These compounds showed potent activity in breast cancer cells and low toxicity in non-cancerous cells. Mechanistic studies demonstrated that these compounds inhibit tubulin polymerization and induce apoptosis, making them potential candidates for the development of novel cancer therapeutics.
Article
Oncology
Patricia Hannon Barroeta, Maureen J. O'Sullivan, Daniela M. Zisterer
Summary: Malignant rhabdoid tumour (MRT), a rare and aggressive childhood malignancy, is highly resistant to chemotherapy. This study investigates the role of the antioxidant defense system involving glutathione (GSH) and Nrf2 in MRT cells' response to cisplatin treatment. Results suggest that targeting the Nrf2/GSH antioxidant system may be a potential therapeutic strategy to overcome chemoresistance in rhabdoid tumours.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Review
Virology
Shubhangi Kandwal, Darren Fayne
Summary: The majority of SARS-CoV-2 therapeutic development work has been focused on targeting spike protein, viral polymerase, and proteases. However, these proteins are prone to mutation and drug resistance. Therefore, it is necessary to target other viral proteins, such as NSPs, and the conserved residues of these proteins.
Article
Chemistry, Medicinal
Shu Wang, Azizah M. Malebari, Thomas F. Greene, Shubhangi Kandwal, Darren Fayne, Seema M. Nathwani, Daniela M. Zisterer, Brendan Twamley, Niamh M. O'Boyle, Mary J. Meegan
Summary: A series of novel analogues of combretastatin A-4 were designed and synthesised as colchicine-binding site inhibitors. These compounds showed significant antiproliferative activities in breast cancer cells and inhibited tubulin assembly. Compound 9q was found to target tubulin, resulting in cellular apoptosis and mitotic catastrophe in MCF-7 cells. In silico molecular docking supported the interaction between the compounds and the colchicine-binding domain of tubulin. Compound 9q has potential as a lead compound for the development of new antitumour agents.
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)
