Article
Biochemistry & Molecular Biology
Manel Ben Hassen, Dhouha Msalbi, Badr Jismy, Fares Elghali, Sami Aifa, Hassan Allouchi, Mohamed Abarbri, Fakher Chabchoub
Summary: A series of new [1,2,4]triazolo[4,3-a]pyrimidine derivatives were synthesized using a one-pot three-component synthesis. The structures of the compounds were confirmed by various analyses. The compounds were evaluated for their antitumor activity and displayed promising results against cancer cell lines.
Article
Chemistry, Multidisciplinary
Qiuyue Zhang, Xuexuan Wu, Hengheng Zhang, Qiuyu Wu, Min Fu, Liwen Hua, Xinyue Zhu, Yuqi Guo, Lianshan Zhang, Qidong You, Lei Wang
Summary: The normal phosphorylation state of proteins is crucial for their function. Hyperphosphorylation of oncoproteins, such as ASK1, can lead to diseases, including gastric cancer. In this study, researchers designed a phosphatase recruitment chimera (PHORC) called DDO3711 to specifically accelerate the dephosphorylation of p-ASK1T838 using a proximity-mediated effect. DDO3711 effectively reduced the level of p-ASK1T838 in vitro and in vivo, showing promising antiproliferative activity against MKN45 cells. This study highlights the potential of PHORCs in regulating abnormal phosphorylation of oncoproteins.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
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
Biochemistry & Molecular Biology
Raj Kamal, Ravinder Kumar, Vipan Kumar, Jitender K. Bhardwaj, Priyanka Saraf, Ajay Kumar, Kritika Pandit, Satwinderjeet Kaur, Prabhakar Chetti, Satyajit Beura
Summary: In this study, eleven novel [1,2,4]triazolo[4,3-a]pyrimidines were synthesized efficiently using DIB as the hypervalent iodine(III) reagent, and the regiochemistry of the final products was established through single crystal and X-ray crystallographic analysis. The synthesized compounds showed significant cytotoxicity against human osteosarcoma bone cancer and breast cancer cell lines, with compound 2g identified as a potent apoptotic inducer.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Biochemistry & Molecular Biology
Pinky Vishwakarma, Noor Fatima Siddiqui, Shikha Thakur, Hemant Jadhav
Summary: This study explores the inhibition of PI3K by FDA-approved drugs with fused pyrimidine scaffold using computational techniques, and identifies Lapatinib as a pan-class I PI3K inhibitor and Dipyridamole as a gamma isoform-specific PI3K inhibitor.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Medicinal
Asma Bourafai-Aziez, Mohammed Benabderrahmane, Hippolyte Paysant, Louis-Bastien Weiswald, Laurent Poulain, Ludovic Carlier, Delphine Ravault, Marie Jouanne, Gael Coadou, Hassan Oulyadi, Anne-Sophie Voisin-Chiret, Jana Sopkova-de Santos Oliveira, Muriel Sebban
Summary: Experimental validation of drug candidates for Mcl-1 inhibition revealed that Deferasirox showed higher biological activity compared to Torsemide, efficiently and selectively inhibiting the anti-apoptotic activity of Mcl-1. NMR studies and biological assays provided detailed characterization of the binding mode and affinity between Deferasirox and Mcl-1.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2021)
Article
Chemistry, Multidisciplinary
Papisetti Venkatesham, Mansi Kalonia, Akanksha Ashok Sangolkar, Anwita Mudiraj, Phanithi Prakash Babu, Rajeswar Rao Vedula
Summary: A novel one-pot synthesis method for potential anticancer triazolopyrimidines was reported. The synthesized compounds showed concentration dependent inhibition against breast cancer cells, and one compound exhibited good binding interaction with amino acid residues in molecular docking simulation.
Article
Biochemistry & Molecular Biology
Essmat M. El-Sheref, Stefan Braese, Hendawy N. Tawfeek, Fatmah Ali Alasmary, Bahaa G. M. Youssif
Summary: The reaction between 4-azido-quinolin-2(1H)-ones and active methylene compounds was studied, leading to the synthesis of a series of 4-(1,2,3-triazol-1-yl)quinolin-2(1H)-ones. Compounds 3f-j showed potent antiproliferative activity and exhibited potential as multi-target inhibitors of EGFR, BRAF(V600E), and EGFR(T790M). Moreover, compounds 3g and 3h demonstrated caspase activation, down-regulation of antiapoptotic Bcl2, and promising antioxidant activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Harichandra D. Tagad, Jordan Brito, Alexander Marin, Christian Buckley, Haoyu Wang, Jingyu Sun, Svetlana A. Sukhishvili, Hongjun Wang, Alexander K. Andrianov
Summary: Advanced multifunctional biomaterials require selective patterns against biological targets, which can be achieved by combining complementary methodologies. This study focused on synthesizing water-soluble anionic macromolecules with the polyphosphazene backbone and nanoassembling them onto fluorinated polyphosphazene surfaces using the layer-by-layer technique. The 4-MU-functionalized fluoro-coatings exhibited a strong antiproliferative effect on vascular smooth muscle cells and fibroblasts while being non-toxic to endothelial cells. These coatings show potential for applications in restenosis-resistant coronary stents and artificial joints.
Article
Biochemistry & Molecular Biology
Mona K. Younis, Islam A. Khalil, Nancy S. Younis, Rasha R. Fakhr Eldeen, Rana M. Abdelnaby, Reem A. Aldeeb, Amal A. Taha, Doaa H. Hassan
Summary: This study aimed to evaluate the antiproliferative effects of an aceclofenac/citronellol oil nanoemulsion on melanoma. The nanoemulsion exhibited potent cytotoxicity and pro-apoptotic effects, with a lower IC50 value compared to aceclofenac or citronellol alone. In silico studies provided insights into the molecular mechanism underlying the observed antitumor activity.
Article
Multidisciplinary Sciences
Xue Zhang, Lingling Huang, Ruizhe Zhao, Hongqiang Zhou, Xin Li, Guangzhou Geng, Junjie Li, Xiaowei Li, Yongtian Wang, Shuang Zhang
Summary: In this paper, the principle of generating diverse geometric patterns using a linear combination of basis functions is introduced. A new type of Dammann vortex metasurface (DVM) is proposed to create an array of diffraction-multiplexed vortex patterns based on three custom-defined basis patterns. This research has important implications for applications such as orbital angular momentum encryption and quantum entanglement.
Article
Chemistry, Medicinal
Gennaro Riccio, Kevin A. Martinez, Jesus Martin, Fernando Reyes, Isabella D'Ambra, Chiara Lauritano
Summary: Jellyfish, commonly eaten in eastern countries, have been found to have potential antiproliferative activity, making them a potential new source of antiproliferative drugs.
Article
Chemistry, Medicinal
Lamya H. H. Al-Wahaibi, Essmat M. M. El-Sheref, Mohamed M. M. Hammouda, Bahaa G. M. Youssif
Summary: Novel 4-((quinolin-4-yl)amino)-thia-azaspiro[4.4/5]alkan-3-ones were synthesized via a one-step reaction between 4-(2-cyclodenehydrazinyl)quinolin-2(1H)-one and thioglycolic acid catalyzed by thioglycolic acid. The newly obtained compounds were characterized by NMR, mass spectra, and elemental analyses. Among them, compounds 6b, 6e, and 7b showed the most potent antiproliferative effects.
Article
Biochemistry & Molecular Biology
Fatma A. M. Mohamed, Hesham A. M. Gomaa, O. M. Hendawy, Asmaa T. Ali, Hatem S. Farghaly, Ahmed M. Gouda, Ahmed H. Abdelazeem, Mostafa H. Abdelrahman, Laurent Trembleau, Bahaa G. M. Youssif
Summary: The new series of EGFR inhibitors showed promising antiproliferative activity against cancer cell lines, with para-substituted phenethyl derivatives displaying superior activity. Some compounds also exhibited potential EGFR inhibitory activity, modulation of apoptosis-related proteins, and cell cycle arrest effects.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Antonino N. Fallica, Valeria Sorrenti, Agata G. D'Amico, Loredana Salerno, Giuseppe Romeo, Sebastiano Intagliata, Valeria Consoli, Giuseppe Floresta, Antonio Rescifina, Velia D'Agata, Luca Vanella, Valeria Pittala
Summary: Novel HO-1 inhibitors were designed and synthesized, showing potent anticancer activity against various cancer cells, with compound 7l demonstrating the best performance by reducing cell invasiveness through modulation of HO-1 expression.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Shuai Wang, Dandan Shen, Lijie Zhao, Xiaohan Yuan, Jialing Cheng, Bin Yu, Yichao Zheng, Hongmin Liu
CHINESE CHEMICAL LETTERS
(2020)
Article
Chemistry, Multidisciplinary
Xiaohan Yuan, Shuai Wang, Jialing Cheng, Bin Yu, Hong-Min Liu
CHINESE CHEMICAL LETTERS
(2020)
Article
Chemistry, Medicinal
Xiao-Jing Shi, Shuai Wang, Xiao-Jing Li, Xiao-Han Yuan, Li-Juan Cao, Bin Yu, Hong-Min Liu
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Chemistry, Medicinal
Shuai Wang, Xu-Bin Ma, Xiao-Han Yuan, Bin Yu, Yi-Chao Xu, Hong-Min Liu
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Review
Chemistry, Medicinal
Shuai Wang, Xiao-Han Yuan, Sai-Qi Wang, Wen Zhao, Xiao-Bing Chen, Bin Yu
Summary: Considerable progress has been achieved in the development of anticancer agents in recent decades, with pyrimidine-fused bicyclic heterocycles showing potential for clinical treatment. New anticancer agents have been produced from natural and synthetic sources, with a focus on improving therapeutic efficacy for various cancers.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Shuai Wang, Sai-Qi Wang, Qiu-Xu Teng, Linlin Yang, Zi-Ning Lei, Xiao-Han Yuan, Jun-Feng Huo, Xiao-Bing Chen, Mengru Wang, Bin Yu, Zhe-Sheng Chen, Hong-Min Liu
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Chemistry, Medicinal
Jin-Ling Huo, Shuai Wang, Xiao-Han Yuan, Bin Yu, Wen Zhao, Hong-Min Liu
Summary: Compound 6i showed potent anti-proliferative activity against MGC-803 with good safety in vivo. Mechanistic studies revealed that 6i induced apoptosis in MGC-803 cells through multiple pathways, suggesting its potential as a template for anti-cancer agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Shuai Wang, Sai-Qi Wang, Qiu-Xu Teng, Zi-Ning Lei, Zhe-Sheng Chen, Xiao-Bing Chen, Hong-Min Liu, Bin Yu
Summary: The triazolo[1,5-a]pyrimidine derivative WS-898 was discovered as a highly effective ABCB1 inhibitor capable of reversing PTX resistance in cells. WS-898 inhibited the efflux function of ABCB1, leading to increased intracellular PTX concentration and enhanced drug efficacy. Additionally, WS-898 showed promising results in in vivo PTX sensitization without causing obvious toxicity.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Qingqing Hao, Shuai Wang, Wenjuan Huang, Yinxiang Zhang, Christophe Pannecouque, Erik De Clercq, Fener Chen
Summary: In this study, novel sulfinylsubstituted analogs were designed to optimize the activity of HEPT as nonnucleoside HIV-1 reverse transcriptase inhibitors. Most of the compounds showed moderate to strong activity against wild-type HIV-1 strain, and some exhibited higher sensitivity towards clinically relevant mutant viruses. Molecular modeling studies were conducted to understand the biological activity of these compounds, providing structural insights for future optimization of HEPT.
BIOORGANIC CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Shuai Wang, Fen-Er Chen
Summary: Inhibition of the MDM2-p53 protein-protein interaction using small-molecule inhibitors is a promising strategy for cancer therapy. Many highly potent and selective small-molecule MDM2 inhibitors have been discovered and are currently undergoing different clinical trials. This review provides an overview of the function of MDM2 and the identification, optimization, preclinical, and clinical studies of clinical-stage MDM2 inhibitors. It also discusses challenges, potential toxicity, and future perspectives, which will guide the design of new small-molecule MDM2 inhibitors.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Xin Jin, Li-Min Zhao, Shuai Wang, Wen-Juan Huang, Yin-Xiang Zhang, Christophe Pannecouque, Erik De Clercq, Fen-Er Chen
Summary: Recent studies have discovered that compound JX-7 has significant inhibitory activity against HIV-1; however, its high cytotoxicity prevented its further development as a clinical candidate. To improve safety, researchers replaced a part of JX-7 with biphenyl, resulting in compound 4ab. This new compound showed lower cytotoxicity and maintained strong anti-HIV-1 activity against multiple mutant strains and wild-type HIV-1.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Ruo-Lan Zhou, Zhiran Ju, Christophe Pannecouque, Erik De Clercq, Shuai Wang, Fen-Er Chen
Summary: In this study, novel cyclopropyl-substituted HEPT analogs were developed to improve their potency and safety as non-nucleoside inhibitors of HIV-1 reverse transcriptase. Compound 9h exhibited significantly increased inhibitory activity against wild-type HIV-1 (EC50=0.017μM) compared to the lead compound 2. It also showed reduced cytotoxicity with a higher selectivity index (SI>2328) and promising pharmacokinetics profiles.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Ya-Li Sang, Christophe Pannecouque, Erik De Clercq, Shuai Wang, Fen-Er Chen
Summary: A series of novel biphenyl-DAPY derivatives were developed using the fragment-hopping strategy to enhance the anti-resistance efficacy of a non-nucleoside reverse transcriptase inhibitor (NNRTI). Most of the compounds exhibited improved anti-HIV-1 potency, with compound 8r showing exceptional potency against wild-type HIV-1 and mutant strains. The new DAPY analogue had lower cytotoxicity, higher selectivity index, and favorable pharmacokinetic properties, making it a potential candidate for HIV treatment.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Shuai Wang, Lichong Gong, Georges El Fakhri, Junfeng Wang
Summary: Efficient synthesis of 6,6'-diamido-2,2'-dipicolylamines (DA-DPAs) for phosphate anion sensing via pre-formed metal complexes was reported in this study. The design was based on retrosynthetic analysis, enabling functionalized DA-DPAs to be obtained with satisfactory yields and high purity using the Boekelheide rearrangement. Additionally, all intermediates could be easily purified by silica gel column chromatography.
NEW JOURNAL OF CHEMISTRY
(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)