Article
Pharmacology & Pharmacy
Anife Ahmedova, Rositsa Mihaylova, Silviya Stoykova, Veronika Mihaylova, Nikola Burdzhiev, Viktoria Elincheva, Georgi Momekov, Denitsa Momekova
Summary: Pt(IV) complexes formed by linking pyrene butyric acid with cisplatin exhibit high anticancer potency against leukemia cells and multidrug-resistant derivatives, while showing low toxicity to healthy cells. The larger bis-pyrene complex is found to potentially be trapped in the cytoskeleton, limiting its cytotoxicity to adherent cells.
Article
Engineering, Biomedical
Maria Sancho-Albero, Giorgio Facchetti, Nicolo Panini, Marina Meroni, Ezia Bello, Isabella Rimoldi, Massimo Zucchetti, Roberta Frapolli, Luisa De Cola
Summary: Platinum-based chemotherapy is the standard first-line treatment for various types of cancer, including malignant pleural mesothelioma. This study presents a strategy using a breakable nanocarrier to stabilize, transport, and release a platinum(IV) prodrug, which is activated by the presence of glutathione in neoplastic cells. In vitro and in vivo experiments demonstrate the successful release and activation of the Pt-based drug inside cancer cells, leading to a significant reduction in tumor growth.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Chemistry, Inorganic & Nuclear
Juan Sanchez-Camacho, Sonia Infante-Tadeo, Ana C. Carrasco, Stefano Scoditti, A'lvaro Martinez, Fabienne Barroso-Bujans, Emilia Sicilia, Ana M. Pizarro, Luca Salassa
Summary: In this study, two new asymmetric Pt(IV) derivatives were designed and synthesized, which could be effectively activated into toxic Pt(II) species by incubation with nicotinamide adenine dinucleotide, sodium ascorbate, and glutathione in the dark and under light irradiation. One of the derivatives displayed enhanced toxicity in MDA-MB-231 breast cancer cells preincubated with ascorbate, suggesting selective triggering of oxaliplatin generation through redox activation. Covalent binding of the flavin to the Pt complex was shown to be pivotal for this effect.
INORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Zhouyang Huang, A. Paden King, James Lovett, Barry Lai, Joshua J. Woods, Hugh H. Harris, Justin J. Wilson
Summary: The photophysical and photochemical properties of two Pt(iv)Re(i) conjugates were studied and found to exhibit modest photocytotoxicity against ovarian cancer cells. X-ray fluorescence microscopy revealed colocalization of Pt and Re in cells, whether or not they had been irradiated. This work highlights the potential of photoactivated multilimetallic agents for cancer treatment.
CHEMICAL COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Ruchika Ojha, Peter C. Junk, Alan M. Bond, Glen B. Deacon
Summary: Pt-IV coordination complexes were synthesized by oxidizing the antitumor agent [Pt-II(p-BrC6F4)NCH2CH2NEt2}Cl(py)]. Experimental data showed that excess H2O2 and elevated temperature favored the oxidation of the ligand, while a smaller amount of H2O2 at room temperature favored the oxidation of the metal, resulting in the formation of platinum(IV) complexes.
Article
Chemistry, Inorganic & Nuclear
Bin-Bin Pan, Hui-Zhong Liu, Wei-Han Meng, Xun-Cheng Su
Summary: This study investigated the interaction between a platinum(iv) complex and alpha-synuclein (α-S) using high-resolution NMR spectroscopy and mass spectrometry. The results showed that the Pt(iv) complex was able to oxidize specific methionine residues in α-S under physiological conditions. These findings are important for understanding the oxidative modification of α-S.
INORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Chemistry, Inorganic & Nuclear
Cinzia Imberti, Jamie Lok, James P. C. Coverdale, Oliver W. L. Carter, Millie E. Fry, Miles L. Postings, Jana Kim, George Firth, Philip J. Blower, Peter J. Sadler
Summary: A novel photoactivatable Pt(IV) diazido anticancer agent with a pendant deferoxamine (DFO) siderophore for radiometal chelation was synthesized, and its in vivo behavior was studied using radionuclide imaging. The results showed that the Pt-succ-DFO complex had photoactivation properties and photocytotoxicity in cancer cells. PET imaging in healthy mice exhibited a promising biodistribution profile, suggesting the potential of this agent for clinical development. This research provides important insights into the development of light-activated agents.
INORGANIC CHEMISTRY
(2023)
Article
Chemistry, Inorganic & Nuclear
Stefano Scoditti, Gloria Mazzone, Nico Sanna, Emilia Sicilia
Summary: This study presents an in-depth computational investigation into the ability of a recently proposed multi-action Ru(II)-Pt(IV) conjugate to act as a photosensitizer in photodynamic therapy (PDT) and chemo-therapeutic drugs. The results show that the investigated complex is capable of releasing a light-absorbing chromophore for use in PDT, and it can also generate cytotoxic reactive oxygen species.
INORGANIC CHEMISTRY
(2022)
Article
Chemistry, Physical
Stefano Scoditti, Eslam Dabbish, German E. Pieslinger, Elixabete Rezabal, Xabier Lopez, Emilia Sicilia, Luca Salassa
Summary: The mechanism for the photocatalytic activation of Pt(iv) anticancer prodrugs by riboflavin in the presence of NADH has been investigated. The results demonstrate that riboflavin accelerates the hydride transfer from NADH to riboflavin in the excited state, and facilitates the reduction of Pt(iv) complexes via an inner sphere mechanism.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2022)
Article
Chemistry, Inorganic & Nuclear
Jiafan Lin, Jishuai Zhang, Ziqi Ma, Xiaoqin Wu, Fuyi Wang, Yao Zhao, Kui Wu, Yi Liu
Summary: The interaction between a photoactivatable Pt(iv) prodrug and human telomeric DNA was studied. Two major mono-platinated DNA adducts were detected, with trans-[Pt-II(N-3)(py)(2)](+) and trans-[Pt-II(py)(2)](2+) as the bound Pt moieties. The platination sites were found to be G(6) and A(3) in one adduct, and a potential intrastrand crosslink was speculated after G(4) and G(6) in the other adduct. Minor platinated adducts and oxidized DNA adducts were also observed. These results provide valuable chemical information about the photoreaction between photoactivatable Pt(iv) anticancer prodrugs and human telomeric DNA.
DALTON TRANSACTIONS
(2023)
Review
Biochemistry & Molecular Biology
Daniil Spector, Olga Krasnovskaya, Kirill Pavlov, Alexander Erofeev, Peter Gorelkin, Elena Beloglazkina, Alexander Majouga
Summary: This review summarizes the research on the development of Pt(IV) prodrugs with NSAIDs as axial ligands, their cytotoxic action and anti-inflammatory activity mechanism studies, structure-activity ratio, and therapeutic efficacy. The chemo-anti-inflammatory strategy aims to efficiently deliver cytotoxic metabolites and NSAIDs intracellularly in tumor cells to reduce side effects and increase therapeutic efficacy. Studies have shown high therapeutic efficacy both in vitro and in vivo.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Jorge Leal, Lucia Santos, Diego M. Fernandez-Aroca, J. Vicente Cuevas, M. Angeles Martinez, Anna Massaguer, Felix A. Jalon, M. Jose Ruiz-Hidalgo, Ricardo Sanchez-Prieto, Ana M. Rodriguez, Gregorio Castaneda, Gema Dura, M. Carmen Carrion, Silvia Barrabes, Blanca R. Manzano
Summary: The study synthesized a series of chloride Pt(II) and Pt(IV) compounds, and investigated their cytotoxic properties against different cell lines, revealing a clear relationship between the type of ligand and anti-proliferative properties, demonstrating a positive effect of the NH2 group on activity, and confirming DNA as a target leading to cell death by apoptosis.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2021)
Review
Pharmacology & Pharmacy
Dongqin Xia, Wenjie Li, Ce Tang, Juan Jiang
Summary: Cancer is increasing in developing countries with unsatisfactory outcomes from traditional cancer treatments. Traditional Chinese medicine (TCM) components, such as Astragaloside IV (AS-IV), have shown significant anticancer activities. AS-IV has various effects, including modulation of enzyme activities, cell cycle arrest, apoptosis and autophagy induction, and suppression of cancer progression. This article reviews the bioavailability, anticancer activity, and mechanism of AS-IV and provides suggestions for further research.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Anli Gao, Yaxi Wu, Juan Yu, Hongyu Gong, Jing Jiang, Caihong Yang, Weiping Liu, Chen Qing
Summary: Two new Pt(iv) complexes with mesylate as the outer sphere anion were synthesized. Both complexes have excellent water-solubility and anticancer activity. SPt-2 showed higher in vitro anticancer activity against three human cancer cell lines and stronger antitumor efficacy in a mouse colon carcinoma model compared to oxaliplatin. This complex has the potential to be developed as a prodrug for oxaliplatin.
RSC MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Mohamed M. El-Bendary, Tamer S. Saleh, Mansour M. Alomari, Ehab M. M. Ali, Bambar Davaasuren, Mariusz Jaremko, Bandar A. Babgi
Summary: A new Pt(IV) complex was synthesized by treating an aqueous acetonitrile solution of chloroplatinic acid hydrate H2PtCl6.xH(2)O and pyridine-2-carbaldehyde-oxime (paOH) with potassium thiocyanate at room temperature. The complex was characterized and its crystallographic structure was determined. In addition, the complex exhibited cytotoxicity against different cancer cell lines and catalytic activity in an oxidation reaction. The luminescence behavior of the complex was also investigated.
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)