Article
Chemistry, Medicinal
Shannon Pecnard, Olivier Provot, Helene Levaique, Jerome Bignon, Laurie Askenatzis, Francois Saller, Delphine Borgel, Sophie Michallet, Marie-Catherine Laisne, Laurence Lafanechere, Mouad Alami, Abdallah Hamze
Summary: A series of cyclic bridged analogs of isocombretastatin A-4 with compound 42 showed high antiproliferative activity against a panel of cancer cell lines, as well as strong activity against colon-carcinoma cells and MDR1-overexpressing K562R cell line. Compound 42 also effectively inhibited tubulin polymerization, induced cell cycle arrest, and caused caspase-induced apoptosis in K562 cells. Additionally, compound 42 was significantly less cytotoxic in non-cancer cells compared to isoCA-4.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Applied
Yuangang Xu, Shuaiqi Wang, Dongxue Li, Pengcheng Wang, Qiuhan Lin, Ming Lu
Summary: A safer, convenient, and scalable synthesis method for 3,4-bis(4-nitro-1,2,5-oxadiazol-3-yl)-1,2,5-oxadiazole-2-oxide (BNFF or DNTF) is described. The obtained products were fully characterized and confirmed by single-crystal X-ray diffraction. The optimized tandem nitration-cyclization reaction process and thermal stability of the reaction system were studied. 3-Amino-4-(carboxymethyl)furazan is oxidized and treated with dilute mixed acid (HNO3 and H2SO4) to obtain BNFF with a yield of 52% and a purity of 99% after liquid chromatography analysis.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2023)
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
Chemistry, Medicinal
Gjorgji Atanasov, Rusi I. Rusew, Vladimir M. Gelev, Christo D. Chanev, Rosica Nikolova, Boris L. Shivachev, Ognyan I. Petrov, Margarita D. Apostolova
Summary: In this study, a series of 26 new styryl-2(3H)-benzothiazolone analogs of combretastatin-A4 (CA-4) were synthesized, characterized, and tested for their biological activities. Compound 26Z showed the most potent cytotoxic activity against EA.hy926 cells and demonstrated anti-vasculogenic effects. Furthermore, 26Z exhibited anti-proliferative activity in CA-4 resistant cells and induced G2/M arrest and mitotic spindle multipolarity, suggesting its potential as a new chemotherapeutic agent with further investigation needed.
Article
Chemistry, Medicinal
Ahmed M. Shawky, Faisal A. Almalki, Ashraf N. Abdalla, Bahaa G. M. Youssif, Maha M. Abdel-Fattah, Fatima Hersi, Hany A. M. El-Sherief, A. Ibrahim Nashwa, Ahmed M. Gouda
Summary: In this study, a series of thiazolidin-4-one-based derivatives were designed as potential anticancer agents by combining the pharmacophoric features of COX inhibitors and tubulin polymerization inhibitors. The synthesized compounds exhibited significant cytotoxic activity against cancer cell lines, as well as inhibitory effects on tumor growth and migration. They also demonstrated moderate COX-2 inhibitory activity and anti-inflammatory effects, with better gastrointestinal safety profiles.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Sultan Nacak Baytas
Summary: Cancer, a leading cause of fatality worldwide, is being extensively researched for therapeutic strategies. Advances in molecular sciences and high throughput techniques have identified microtubules as attractive targets for cancer therapy. The development of new microtubule-targeting agents, particularly analogues of combretastatin A-4, has been a focus of research since 2015.
CURRENT MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Pei-Yi Tsai, Gong-Siang Hu, Po-Hsun Huang, Huei-Lin Jheng, Chi-Hsuan Lan, You-Sin Chen, Jia-Ming Chang, Shih-Hsien Chuang, Jiann-Jyh Huang
Summary: This paper reports the design and synthesis of a novel anticancer agent, with compound 6q demonstrating significant antiproliferative activity against various cancer cells and displaying in vivo activity in nude mice. Compound 6q has potential as a lead compound for further optimization in anticancer drug development.
JOURNAL OF THE CHINESE CHEMICAL SOCIETY
(2021)
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.
Review
Biochemistry & Molecular Biology
Suresh Paidakula, Srinivas Nerella, Shravankumar Kankala, Ranjith Kumar Kankala
Summary: This article systematically summarizes the recent trends and developments in anticancer drug design and discovery using CA-4 analogs as tubulin inhibiting agents.
CURRENT MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Raquel Alvarez, Laura Aramburu, Consuelo Gajate, Alba Vicente-Blazquez, Faustino Mollinedo, Manuel Medarde, Rafael Pelaez
Summary: 39 new compounds of isocombrtastatin analogs have been synthesized to improve water solubility by replacing the 3,4,5-trimethoxyphenyl ring, and it is found that 2-chloro-6-methylsulfanylpyridines are more successful replacements than 2,6-bis(methylsulfanyl) pyridines with highly potent tubulin inhibitors and cytotoxic compounds.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Samar El-Kalyoubi, Samiha A. El-Sebaey, Ahmed A. El-Sayed, Moustafa S. Abdelhamid, Fatimah Agili, Sherin M. Elfeky
Summary: Nanotechnology-based strategies can overcome the limitations of conventional cancer therapies. Novel pyrimidine Schiff bases were employed to synthesize selenium nanoparticle forms, which exhibited greater inhibitory effects compared to normal-sized compounds and 5-fluorouracil. Compound 4 and its nanoform 4NPs showed effective anti-proliferative activity against multiple cancer cell lines, with 4NPs exhibiting increased efficacy and selectivity.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Rui Yang, Huimin Jia
Summary: This paper demonstrates that a 4-regular plane graph G is a {(3,4),4}-fullerene graph with eight triangular faces and other quadrangular faces. The anti-Kekule number a_k_G of G is the smallest cardinality of anti-Kekule sets. It is shown that when G is an element of H-1, then a_k_G = 4, and a condition is given to determine whether the anti-Kekule number of graph G is 4 or 5 when G is an element of H-2.
FRONTIERS IN CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Khaled El-Adl, Abdel-Ghany A. El-Helby, Rezk R. Ayyad, Hazem A. Mahdy, Mohamed M. Khalifa, Hamdy A. Elnagar, Ahmed B. M. Mehany, Ahmed M. Metwaly, Mostafa A. Elhendawy, Mohamed M. Radwan, Mahmoud A. ElSohly, Ibrahim H. Eissa
Summary: By designing and synthesizing new quinazoline-4(3H)-one derivatives, and conducting cytotoxicity studies, it was found that some compounds have significant inhibitory effects on cancer cells, with compound 16(f) showing the most promising activity, outperforming the positive controls across multiple cell lines.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Yufeng Li, Jiangman Sun, Mingxing Chen, Shushu Miao, Ming Liu, Yongjie Ma, Guan Wang, Xinggui Gu, Ben Zhong Tang
Summary: Luminescent materials that emit both visible and near-infrared light have the potential to enhance anti-counterfeiting measures by providing covert information that can only be detected with special devices.
ADVANCED FUNCTIONAL MATERIALS
(2022)
Article
Biochemistry & Molecular Biology
Eric A. Zizzi, Marco Cavaglia, Jack A. Tuszynski, Marco A. Deriu
Summary: The study investigated the interaction between human tubulin and four volatile anesthetics, predicting binding sites and affinity rankings through docking and Molecular Dynamics simulations. The simulations suggested a transient interaction between anesthetics and microtubules, with interaction strengths consistent with the potencies of the compounds.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Huan Luo, Yi Wang, Qiuyi Qin, Yihai Wang, Jingwen Xu, Xiangjiu He
Summary: In this study, various anti-inflammatory compounds were isolated from the roots of Morinda officinalis. Among them, two compounds showed significant inhibitory effects on the production of pro-inflammatory factors in macrophages, indicating potential benefits in preventing and reducing inflammatory-associated diseases.
BIOORGANIC CHEMISTRY
(2021)
Article
Toxicology
Jingwen Xu, Zhe Wang, Lianlian Sun, Yi Wang, Yihai Wang, Xiangjiu He
Summary: WT-26 demonstrated superior anti-inflammatory activity compared to its analog Kaurenoic acid, by suppressing the production of inflammatory mediators, activation of NF-κB and MAPKs, reducing ROS overproduction, and attenuating LPS-induced autophagy in macrophages. These findings suggest the potential of WT-26 as a novel therapeutic agent for inflammatory-related diseases.
TOXICOLOGY IN VITRO
(2021)
Article
Biochemistry & Molecular Biology
Jiaming Yao, Zhe Wang, Ru Wang, Yihai Wang, Jingwen Xu, Xiangjiu He
Summary: This study identified several compounds with anti-proliferative or cytotoxic activities from the fruits of Ficus altissima, some of which showed significant inhibitory effects on different tumor cell lines in a concentration-dependent manner, suggesting potential medicinal value.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Xuehai Zhang, Yi Wang, Qiuyi Qin, Yihai Wang, Jingwen Xu, Xiangjiu He
Summary: This study identified anti-neuroinflammatory compounds in lychee seeds, showing potential benefits for neuroinflammatory-associated diseases like Alzheimer's. The compounds exhibited significant activities in inhibiting inflammatory factors and may have therapeutic potential in neuroinflammation.
Article
Biochemistry & Molecular Biology
Jingwen Xu, Yi Wang, Zhe Wang, Yihai Wang, Xiangjiu He
Summary: The study demonstrates that T-17 induces cell cycle arrest, apoptosis, and autophagy in gastric cancer cells independently of p53 status. T-17 triggers apoptosis and autophagy by reducing HMGB1 expression in a p53-independent manner, while its inhibitory effect on cell migration is p53-dependent.
Article
Food Science & Technology
Liangmiao Luo, Yi Wang, Yihai Wang, Jingwen Xu, Xiangjiu He
Summary: This study identified new sterols and a terpenoid, as well as known phytochemicals from mango fruits, showing significant anti-neuroinflammatory activity. Compounds 2 and 5 were found to have the most pronounced effects, acting through the NF-kappa B pathway, indicating the potential health benefits of mango fruits.
JOURNAL OF FUNCTIONAL FOODS
(2021)
Article
Food Science & Technology
Yuying Huang, Jingwen Xu, Yihai Wang, Yanqiong Lei, Yongxin Mai, Xiangjiu He
Summary: The study demonstrated that Q43 extracted from Chinese acorn has anti-neuroinflammatory properties by suppressing nitric oxide and prostaglandin E2 production, reducing pro-inflammatory cytokine secretion, and modulating signaling pathways involved in neuroinflammation and oxidative stress.
JOURNAL OF FUNCTIONAL FOODS
(2021)
Article
Biochemistry & Molecular Biology
Jingwen Xu, Yihai Wang, Yi Wang, Zhe Wang, Xiangjiu He
Summary: The study showed that A-24 induces apoptosis and autophagy in both p53 wild-type and deficient gastric cancer cells, with a significant proliferation inhibition effect on the latter. The p53 status influenced the occurrence of autophagy induced by A-24, but had no effect on ROS-mediated apoptosis. Furthermore, A-24 acted through different pathways in p53 wild-type and deficient cells, suggesting its potential as a phytotherapeutic candidate for gastric cancer treatment.
CHEMICO-BIOLOGICAL INTERACTIONS
(2021)
Article
Agriculture, Multidisciplinary
Jiming Li, Ru Wang, Yihai Wang, Jia Zeng, Zeyong Xu, Jingwen Xu, Xiangjiu He
Summary: This study explored the anti-inflammatory phytochemicals of Chinese olive fruit and discovered nine pairs of new benzofuran neolignans. These compounds exhibited pronounced inhibitory effects on nitric oxide production and some of them exerted anti-inflammatory effects by blocking the nuclear translocation of NF-kappa B.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Plant Sciences
Zhe Wang, Jingwen Xu, Yihai Wang, Limin Xiang, Xiangjiu He
Summary: This study aimed to investigate the potential anti-proliferative activity and anti-tumor mechanism of Tupistra chinensis Baker (TCS) on gastric cancer. The results showed that TCS exhibited significant anti-gastric cancer effects in both in vitro and in vivo experiments.
JOURNAL OF ETHNOPHARMACOLOGY
(2021)
Article
Plant Sciences
Wenxiang Zhang, Qiuyi Qin, Yihai Wang, Jia Zeng, Yongxin Mai, Jingwen Xu, Xiangjiu He
Summary: Eighteen oleanane-type triterpenoids were isolated from Chinese oak seeds and showed significant anti-neuroinflammatory activity.
PHYTOCHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Yi Wang, Jingwen Xu, Yihai Wang, Limin Xiang, Xiangjiu He
Summary: This study investigated the mechanism of action of steroidal saponin S-20 isolated from black nightshade berries on multidrug resistant K562/ADR cells. The results showed that S-20 induces autophagic cell death in K562/ADR cells and inhibits drug resistance protein expression through the activation of ERK pathway.
Article
Biochemistry & Molecular Biology
Wenjing Ma, Siyu Wang, Yihai Wang, Jia Zeng, Jingwen Xu, Xiangjiu He
Summary: Seven undescribed Amaryllidaceae alkaloids and seven known alkaloids were isolated from the bulbs of Hymenocallis littoralis. These alkaloids exhibited antiproliferative activity and the potential to inhibit tumor cell migration, and could induce apoptosis.
Review
Biochemistry & Molecular Biology
Jingwen Xu, David A. Gewirtz
Summary: Cisplatin, a first-line chemotherapy drug for cancer, has been found to induce autophagy in response to cancer treatments. Autophagy has been increasingly recognized as a critical factor in tumor cell death and chemoresistance. This review discusses the mechanisms of resistance to cisplatin and explores the role of autophagy in both cisplatin-sensitive and resistant cells, as well as the potential dual outcomes of combining autophagy inhibitors with cisplatin. The goal is to analyze the possible clinical application of combining cisplatin and autophagy inhibitors.
Review
Biochemistry & Molecular Biology
Jingwen Xu, Ahmed M. Elshazly, David A. Gewirtz
Summary: This article explores the nature and function of autophagy induced by microtubule poisons, and speculates on the potential of autophagy inhibition to improve the response to cancer therapy involving these drugs that target microtubule function.
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)
