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Pharmacology & Pharmacy
Santiago Schiaffino-Ortega, Elena Mariotto, Pilar Maria Luque-Navarro, Maria Kimatrai-Salvador, Pablo Rios-Marco, Ramon Hurtado-Guerrero, Carmen Marco, Maria Paz Carrasco-Jimenez, Giampietro Viola, Luisa Carlota Lopez-Cara
Summary: Choline kinase inhibitors have shown promising cytotoxic effects on cancer cells, with certain compounds exhibiting both strong inhibitory activity on the enzyme and potent antiproliferative effects. The structure-activity relationship studies revealed that compounds with the N-atom connected to the linker demonstrated better inhibitory results, while those with the O-atom bounded to the linker showed better antiproliferative activity. Additionally, the length of the linker played a role in the inhibitory effect on the enzyme, with shorter linkers yielding better results.
Article
Biochemistry & Molecular Biology
Paulo Sergio Goncalves Nunes, Gabriel da Silva, Sofia Nascimento, Susimaire Pedersoli Mantoani, Peterson de Andrade, Emerson Soares Bernardes, Daniel Fabio Kawano, Andreia Machado Leopoldino, Ivone Carvalho
Summary: ERK1/2 inhibitors are being explored for their potential to overcome resistance to RAF and MEK kinase inhibitors. A new 4-aminoquinazoline derivative, compound 25a, showed promising activity in BT-20 cells by inducing cell death through lactate dehydrogenase release and necrosis induction. The compound also led to cell cycle arrest and downregulation of key signaling pathways in breast cancer cells.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Aya A. Farahat, Eman M. Samir, Mayssoune Y. Zaki, Rabah A. T. Serya, Hatem A. Abdel-Aziz
Summary: The novel pyrazolo[3,4-b]pyridine compounds exhibit potent antiproliferative activity against HepG2 and HeLa cells, with compounds 14a and 14d showing the most efficacy. These compounds can also induce cell cycle disturbance and apoptosis in HepG2 cells. Furthermore, compounds 9h and 14d are identified as the most efficient antiproliferative agents in a screening of the NCI 60-cell line panel. Additionally, some compounds show good inhibitory action against the cellular pathway regulator p38 alpha kinase.
ARCHIV DER PHARMAZIE
(2022)
Article
Pharmacology & Pharmacy
Francisco Jose Aguilar-Troyano, Archimede Torretta, Gianluca Rubbini, Alberto Fasiolo, Pilar Maria Luque-Navarro, Maria Paz Carrasco-Jimenez, Guiomar Perez-Moreno, Cristina Bosch-Navarrete, Dolores Gonzalez-Pacanowska, Emilio Parisini, Luisa Carlota Lopez-Cara
Summary: A new treatment strategy for malaria, involving the suppression of host material uptake by the parasite, has shown promising results. Bioisosteric compounds capable of inhibiting Plasmodium falciparum Choline Kinase, particularly one with pyrrolidine substitution, have been identified as effective in reducing parasite development. Further studies are needed to determine the specific molecular target of these compounds.
Article
Pharmacology & Pharmacy
Pablo Garcia-Molina, Alberto Sola-Leyva, Pilar M. Luque-Navarro, Alejandro Laso, Pablo Rios-Marco, Antonio Rios, Daniela Lanari, Archimede Torretta, Emilio Parisini, Luisa C. Lopez-Cara, Carmen Marco, Maria P. Carrasco-Jimenez
Summary: The overexpression of Choline Kinase alpha 1 (ChoK alpha 1) has been associated with cell proliferation, oncogenic transformation, and carcinogenesis, making it a potential target in cancer therapy. Additionally, the choline transporter CTL1 is highly expressed in tumor cell lines. Inhibition of both choline uptake and ChoK alpha 1 activity has been shown to correlate with reduced cell proliferation in cancer cell lines, suggesting both proteins as potential targets for cancer therapy.
Article
Biochemistry & Molecular Biology
Chanokbhorn Phaosiri, Chavi Yenjai, Thanaset Senawong, Gulsiri Senawong, Somprasong Saenglee, La-or Somsakeesit, Pakit Kumboonma
Summary: This study examined the inhibitory activity of twenty newly synthesized derivatives of [6]-shogaol against histone deacetylases. The results showed that some of the derivatives exhibited moderate to good inhibition, with certain compounds displaying selective inhibition against specific isoforms. Among them, the pyrazole products and the Michael adduct with pyridine and benzothiazole demonstrated the highest potency. The most active compound, 5j, showed promising antiproliferative activity against various cancer cell lines.
Article
Pharmacology & Pharmacy
Pilar Maria Luque-Navarro, Elena Mariotto, Marco Ballarotto, Gianluca Rubbini, Francisco Jose Aguilar-Troyano, Alberto Fasiolo, Archimede Torretta, Emilio Parisini, Antonio Macchiarulo, Alejandro Laso, Carmen Marco, Giampietro Viola, Maria Paz Carrasco-Jimenez, Luisa Carlota Lopez-Cara
Summary: This study presents a series of compounds designed based on a known strategy. Some of these compounds show improved enzyme inhibition and antiproliferative effects, with Ff-35 being the most promising compound that inhibits the growth of different tumor cells and induces cell cycle arrest and apoptosis.
Article
Chemistry, Medicinal
Wael Zeinyeh, Yannick J. Esvan, Beatrice Josselin, Mathilde Defois, Blandine Baratte, Stefan Knapp, Apirat Chaikuad, Fabrice Anizon, Francis Giraud, Sandrine Ruchaud, Pascale Moreau
Summary: Haspin is a potential target for the development of anticancer drugs, but current inhibitors show poor selectivity for human kinome. A new inhibitor with excellent activity and selectivity for Haspin has been identified, and its binding mode with Haspin has been determined through crystallography.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Yunqing Li, Marianna Inglese, Suraiya Dubash, Chris Barnes, Diana Brickute, Marta Costa Braga, Ning Wang, Alice Beckley, Kathrin Heinzmann, Louis Allott, Haonan Lu, Cen Chen, Ruisi Fu, Laurence Carroll, Eric O. Aboagye
Summary: This study investigated how hypoxia affects the dynamics of the choline radiotracer [F-18]-D4-FCH, revealing that hypoxia/HIF-1 alpha increases the efflux of phosphorylated radiolabelled choline species, supporting the consideration of efflux in the modelling of radiotracer dynamics.
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
Lamya H. Al-Wahaibi, Mohamed A. Mahmoud, Yaser A. Mostafa, Ali E. Raslan, Bahaa G. M. Youssif
Summary: A new series of piperine-carboximidamide hybrids were developed as cytotoxic agents targeting EGFR, BRAF, and CDK2, and showed promising antiproliferative activity. Several compounds exhibited potent inhibitory effects on cancer cell proliferation, specifically targeting EGFR, BRAFV600E, and CDK2. The study also highlighted the importance of molecular docking and in silico ADME/pharmacokinetic analysis in drug design.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Shilpi Gupta, Shang Eun Park, Saghar Mozaffari, Bishoy El-Aarag, Keykavous Parang, Rakesh Kumar Tiwari
Summary: The hybrid compounds of benzopyran-4-ones and isoxazoles were designed and synthesized, and they exhibited significant antiproliferative activity against multiple cancer cell lines and anti-inflammatory activity. Compound 5a showed selective anticancer activity and the ability to induce apoptosis in cancer cells.
Article
Chemistry, Medicinal
Surendra Kunwar, Soo-Yeon Hwang, Pramila Katila, Tara Man Kadayat, Ah-Reum Jung, Youngjoo Kwon, Eung-Seok Lee
Summary: A series of newly synthesized compounds were tested for their inhibitory activity against topoisomerase II alpha and antiproliferative activity against cancer cell lines, and some compounds showed high activity in both assays. The study also revealed the importance of specific substituents for the activity of these compounds.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Multidisciplinary
Agnieszka Lubek-Nguyen, Marta Olech, Natalia Nowacka-Jechalke, Aleksandra Martyna, Konrad Kubinski, Maciej Maslyk, Marcin Moczulski, Sebastian Kanak
Summary: The crude polysaccharide fraction obtained from Rosa rugosa Thunb. root has shown potential as a functional component for the pharmaceutical or cosmetic industry. It contains water-soluble and -insoluble sugars, with a significant amount of beta-glucans. The polysaccharide fraction has exhibited antioxidant, anti-inflammatory, and slight antiproliferative effects, making it a promising candidate for cosmetic and biomedical purposes.
APPLIED SCIENCES-BASEL
(2022)
Article
Chemistry, Medicinal
Vu Ngoc Toan, Nguyen Dinh Thanh
Summary: A series of substituted N-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)thiosemicarbazones were synthesized and evaluated for cytotoxic activity against several cancer cell lines, showing low toxicity to normal cells. The antiproliferative mechanisms were studied via EGFR inhibition and molecular docking, revealing strong interactions with EGFR tyrosine kinase domain receptor.
MEDICINAL CHEMISTRY RESEARCH
(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)