Article
Microbiology
Mikel Etxebeste-Mitxeltorena, Daniel Plano, Socorro Espuelas, Esther Moreno, Carlos Aydillo, Antonio Jimenez-Ruiz, Juan Carlos Garcia Soriano, Carmen Sanmartin
Summary: Two new series of selenocyanate and diselenide derivatives containing amide moieties were synthesized and evaluated for leishmanicidal activity. Eleven compounds exhibited excellent activity with EC50 values lower than the reference drug miltefosine. The most potent and selective compounds showed high selectivity indices when tested against THP-1 monocytic cells. These derivatives could potentially be leading candidates for leishmanicidal drugs.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Chemistry, Medicinal
Dennis X. Hu, Snahel Patel, Huifen Chen, Shumei Wang, Steven T. Staben, Yoana N. Dimitrova, Heidi Ackerly Wallweber, Joanna Y. Lee, Grace Ka Yan Chan, Christopher J. Sneeringer, Madeleine S. Prangley, John G. Moffat, Kai C. Wu, Leah K. Schutt, Laurent Salphati, Jodie Pang, Erin McNamara, Haochu Huang, Yong Chen, Yunli Wang, Wensheng Zhao, Junghyun Lim, Aditya Murthy, Michael Siu
Summary: A new series of dihydropyr-azolopyrazinone compounds have been identified as potent, selective, and orally bioavailable VPS34 inhibitors through a structure-based design strategy. The study suggests that sustained inhibition of VPS34 kinase activity may not be well tolerated, and the selectivity of VPS34 inhibitors over PIK family kinases is crucial. This research may provide insights for avoiding targeting VPS34 in other ATP-competitive kinase programs.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Inorganic & Nuclear
Tania Hidalgo, David Fabra, Raul Allende, Ana I. Matesanz, Patricia Horcajada, Tarita Biver, Adoracion G. Quiroga
Summary: Cancer is a leading cause of death worldwide, with nearly 10 million deaths in 2020. Palladium complexes have great potential as anticancer agents, offering advantages over platinum drugs such as better speciation control and lower toxicity. This study developed two novel complexes and thoroughly investigated their speciation in solution, demonstrating their stability and behavior towards nucleic acid models and serum proteins. Furthermore, these complexes showed higher efficiency and specificity compared to the benchmark cisplatin drug due to their lower toxicity to healthy cells.
INORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Multidisciplinary
Lu Jiang, Pei Lin Chee, Jian Gao, Ching Ruey Raymond Gan, Cally Owh, Rajamani Lakshminarayanan, Shan Jiang, T. S. Andy Hor, Xian Jun Loh
Summary: The study revealed that the bis-methylphenyl-substituted porphyrins have superior bactericidal activities with low hemotoxicity and good cytotoxicity profile, even in the dark.
CHEMISTRY-AN ASIAN JOURNAL
(2021)
Article
Chemistry, Medicinal
Jimin Xu, Shuizhen Shi, Gang Liu, Xuping Xie, Jun Li, Andrew A. Bolinger, Haiying Chen, Wenbo Zhang, Pei-Yong Shi, Hua Liu, Jia Zhou
Summary: Novel pyrrolo[1,2-a]quinoxaline-based derivatives have been identified as potent and selective Sirt6 activators with low cytotoxicity. These compounds can repress inflammation and cancer cell formation, and also exhibit inhibitory effects on SARS-CoV-2 infection.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Romario Jonas Oliveira, Cosme Silva Santos, Rodrigo Ribeiro Alves Caiana, Kleber Juvenal Silva Farias, Renato Ferreira Almeida Junior, Paula Renata Lima Machado, Antonio Augusto Soares-Paulino, Paulo Henrique Menezes, Juliano Carlo Rufino Freitas
Summary: In this study, O-alkylaryl amidoximes were designed and synthesized as antiproliferative agents targeting PARP-1. The compounds exhibited in vitro antineoplastic activity against MCF-7 and Caco-2 cells, with one compound showing selective toxicity against VERO cells. These synthesized compounds show potential for further development as new antiproliferative drugs.
Article
Chemistry, Multidisciplinary
Donghui Zhang, Chao Shi, Zihao Cong, Qi Chen, Yufang Bi, Junyu Zhang, Kaiqian Ma, Shiqi Liu, Jiawei Gu, Minzhang Chen, Ziyi Lu, Haodong Zhang, Jiayang Xie, Ximian Xiao, Longqiang Liu, Weinan Jiang, Ning Shao, Sheng Chen, Min Zhou, Xiaoyan Shao, Yidong Dai, Maoquan Li, Lixin Zhang, Runhui Liu
Summary: With the quick increase of serious invasive fungal infections and the limited antifungal drugs available, there is an urgent need for potent and selective antifungal agents. Inspired by microbial metabolites, the authors have designed and obtained poly(DL-diaminopropionic acid) (PDAP), a potent antifungal agent that kills fungal cells by penetrating the cytoplasm, generating reactive oxygen, and inducing fungal apoptosis. PDAP displays strong antifungal activity against Candida albicans, negligible hemolysis and cytotoxicity, and no susceptibility to antifungal resistance. In addition, PDAP effectively inhibits fungal biofilm formation and eradicates mature biofilms. In vivo studies have shown that PDAP is safe and effective in treating fungal keratitis, highlighting its potential as a promising new antifungal agent.
Article
Chemistry, Inorganic & Nuclear
Noemi Pagliaricci, Riccardo Pettinari, Fabio Marchetti, Claudio Pettinari, Loredana Cappellacci, Alessia Tombesi, Massimiliano Cuccioloni, Mouna Hadiji, Paul J. Dyson
Summary: In this study, a series of half-sandwich ruthenium(ii) complexes with curcuminoid ligands were prepared and investigated for their cytotoxic activities. The introduction of a long hydrophobic chain by replacing the OH-groups in curcumin and bisdemethoxycurcumin with palmitic acid ester was found to enhance the cytotoxicity. The complexes showed potent and selective cytotoxic activity against ovarian carcinoma cells and their cisplatin-resistant form.
DALTON TRANSACTIONS
(2022)
Article
Cell Biology
Janka Szinyakovics, Fanni Keresztes, Eszter Anna Kiss, Gergo Falcsik, Tibor Vellai, Tibor Kovacs
Summary: Autophagy is a degradation process that breaks down unnecessary cellular components, but its activity declines with age, leading to cellular damage accumulation and cell dysfunction. This is particularly problematic for neurons, and the activation of autophagy could be a potential treatment for neurodegenerative diseases.
Article
Chemistry, Medicinal
Pegi Pavletic, Ana Semeano, Hideaki Yano, Alessandro Bonifazi, Gianfabio Giorgioni, Alessandro Piergentili, Wilma Quaglia, Maria Giovanna Sabbieti, Dimitrios Agas, Giorgio Santoni, Roberto Pallini, Lucia Ricci-Vitiani, Emanuela Sabato, Giulio Vistoli, Fabio Del Bello
Summary: In this paper, new ligands with high affinity and selectivity for D4R were discovered to better understand its role in GBM. The D4R antagonist 24 and biased ligand 29 showed the most potential and induced a decreased viability of GBM cells. Interestingly, these compounds had a greater effect in reducing cell viability compared to temozolomide, the first-choice chemotherapeutic drug in GBM.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Alma Fuentes-Aguilar, Penelope Merino-Montiel, Sara Montiel-Smith, Socorro Meza-Reyes, Jose Luis Vega-Baez, Adrian Puerta, Miguel X. Fernandes, Jose M. Padron, Andrea Petreni, Alessio Nocentini, Claudiu T. Supuran, Oscar Lopez, Jose G. Fernandez-Bolanos
Summary: In this study, a small library of 2-aminobenzoxazole-appended coumarins was designed, synthesized, and evaluated as novel inhibitors of tumour-related CA IX and XII. The structure-activity relationships were established through modifications on substituents and linker length. The compounds exhibited good selectivity towards CA IX and XII and the introduction of a chlorine atom on the coumarin moiety showed the strongest antiproliferative activity.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Francisco J. Hicke, Adrian Puerta, Jelena Dinic, Milica Pesic, Jose M. Padron, Oscar Lopez, Jose G. Fernandez-Bolanos
Summary: Novel mitochondria-targeted compounds, combining a phenethyl alcohol motif with a triphenyl phosphonium scaffold, exhibited strong antiproliferative activities against tumor cells, showing up to 350-fold improvement compared to classical chemotherapeutic agents. These compounds also demonstrated promising selectivity and potency, including towards multidrug resistant cells when co-administered with a pump-efflux inhibitor.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Yiying Wei, Xinxin Xu, Minchuan Jiang, Yongxing Wang, Yang Zhou, Zhen Wang, Zhang Zhang, Fengtao Zhou, Ke Ding
Summary: A new selective GSPT1 degrader was developed, which could effectively degrade GSPT1 and showed good selectivity in the global proteomic profiling study. The compound also displayed good antiproliferative activities and induced cell cycle arrest and apoptosis in U937 cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Inorganic & Nuclear
Linming Li, Ming Zhang, Dianlong Jia, Zhifang Liu, Ning Zhang, Bin Sun, Zhengping Wang, Min Liu, Qingpeng Wang
Summary: The study focuses on developing new chemotherapeutics for anti-metastasis properties. Multi-specific NFA platinum(iv) complexes were designed, synthesized, and evaluated as novel antitumor agents with mechanisms including DNA damage, inflammation inhibition, immunity activation, and angiogenesis suppression. These complexes showed promising antitumor activities with lower toxicity and attractive anti-metastasis performance. They caused serious DNA damage, promoted apoptosis, improved immune response, and suppressed angiogenesis, making them potential anti-proliferative and anti-metastatic drugs.
DALTON TRANSACTIONS
(2022)
Article
Multidisciplinary Sciences
Mohammed Salah Ayou, Yasmin Wahby, Hamida Abdel-Hamid, Marwa M. Abu-Serie, Mohamed Teleb
Summary: This study explores a new approach to induce apoptosis by selectively activating caspase-3 to eliminate tumors. Compounds prepared by optimized Passerini reaction showed highly efficient anticancer activity against cancer cells in vitro. Further mechanistic studies demonstrated the compounds' action through caspase activation and apoptotic induction.
SCIENTIFIC REPORTS
(2022)
