Article
Chemistry, Organic
Fan Ding, Leilei Liang, Jiacan Yao, Bo Wang, Chang Xu, Dandan Liu
Summary: This research presents the total synthesis of (+)-pancratistatin in 10 linear steps using a known aldehyde as a chiral source. The synthetic route involves a highly stereoselective intermolecular Michael addition and intramolecular Henry reaction to construct a cyclohexane ring with 6 successive stereocenters. All of the synthetic steps are reliable and efficient and can be easily scaled up, allowing for pharmacological tests of (+)-pancratistatin. Importantly, this study discovered a new pharmacological mechanism of action where (+)-pancratistatin is able to inhibit the activity of topoisomerase I, suggesting its potential as a new type of Topo I inhibitor.
Article
Biochemistry & Molecular Biology
Manasa Kadagathur, Arbaz Sujat Shaikh, Biswajit Panda, Joel George, Regur Phanindranath, Dilep Kumar Sigalapalli, Nagesh A. Bhale, Chandraiah Godugu, Narayana Nagesh, Nagula Shankaraiah, Neelima D. Tangellamudi
Summary: A series of new compounds were synthesized and evaluated for their anti-tumor activity. Compound 14d showed remarkable activity against multiple cancer cell lines and exhibited selectivity towards lung cancer cells. Further studies revealed that compound 14d inhibited the growth and migration of cancer cells by interacting with DNA and inhibiting Topo I.
BIOORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Shazia Parveen, Farukh Arjmand, Qianfan Zhang, Musheer Ahmad, Arif Khan, Loic Toupet
Summary: In this study, the synthesis and single crystal X-ray structure of Cu(II)-picolinic acid complex, 1 as a potent topoisomerase I inhibitor was reported. Biochemical studies revealed the complex's higher binding propensity towards tRNA, significant inhibitory effect on enzyme catalytic activity, and strong antimicrobial potential. Additionally, DFT and molecular docking studies provided insights into electronic transitions and specific binding preferences at the target site.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Biochemistry & Molecular Biology
Jay Prakash Soni, G. Nikitha Reddy, Ziaur Rahman, Anamika Sharma, Akella Spandana, Regur Phanindranath, Manoj P. Dandekar, Narayana Nagesh, Nagula Shankaraiah
Summary: In this study, a series of new beta-carboline tethered indole-3-glyoxylamide derivatives were synthesized, which showed significant pharmacological properties and prominent cytotoxicity. The compounds exhibited remarkable cytotoxicity against human cancer cell lines, especially melanoma, and showed selective toxicity towards cancer cells compared to normal cells. The compounds induced apoptosis and showed potential as DNA binders and inhibitors of Topoisomerase II. Molecular modeling studies confirmed their excellent DNA intercalation potential. In addition, in silico analysis predicted the promising drug-like properties of the synthesized derivatives.
BIOORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Saibin Zhu, Yeji Wang, Zhongqing Wen, Yanwen Duan, Yong Huang
Summary: The study revealed that Huanglongmycin congener 14 exhibited stronger cytotoxicity against tested cancer cells, and highlighted the critical role of the C-7 ethyl group of 14 in its binding to the DNA-topoisomerase I complex.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Inorganic & Nuclear
Qi-Yan Liu, Yong-Yu Qi, Dai-Hong Cai, Yun-Jun Liu, Liang He, Xue-Yi Le
Summary: Two new copper(II) complexes of sparfloxacin were synthesized and displayed good antitumor activity by inducing apoptosis through DNA damage and loss of mitochondrial functions.
DALTON TRANSACTIONS
(2022)
Article
Biochemistry & Molecular Biology
Kristie D. Goodwin, Mark A. Lewis, Eric C. Long, Millie M. Georgiadis
Summary: Bleomycins are anticancer natural products that bind DNA through intercalation and hydrogen-bonding interactions. The C-terminal tail was found to play a role in directing the intercalation of the bithiazole. Specific bond rotations within the C-terminal domain of the drug were identified and may be relevant for its reorganization and ability to carry out a double-strand DNA cleavage event.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Review
Chemistry, Organic
Chandrakant Sahu, Abhishek Chaurasiya, Pooja A. Chawla
Summary: This article summarizes the significance of nitrogen-containing heterocyclic compounds in medicinal chemistry and their structure-activity relationship, mechanism and docking studies. The importance of DNA topoisomerase II in anticancer drugs is emphasized, calling for further research on topo II or multi-target topo II inhibitors to overcome drug resistance and reduce toxicity.
JOURNAL OF HETEROCYCLIC CHEMISTRY
(2023)
Article
Chemistry, Physical
Seema Kirar, Yeddula Nikhileshwar Reddy, Uttam Chand Banerjee, Jayeeta Bhaumik
Summary: This work designs and synthesizes a series of novel small fluorophores called meso-substituted heterocyclic BODIPYs as phototherapeutic agents. To improve the efficiency in biological applications, biopolymer-based nanoparticles (BODIPY-GNPs) are developed to incorporate BODIPYs in the aqueous system. The BODIPY-GNPs exhibit better physicochemical properties and show photo-inhibition activity towards bacteria and fungi, as well as the ability to intercalate DNA. This study provides a new avenue for designing therapeutic agents in photodynamic therapy.
Article
Multidisciplinary Sciences
Ahmed A. Gaber, Mohamed Sobhy, Abdallah Turky, Wagdy M. Eldehna, Samiha A. El-Sebaey, Souad A. El-Metwally, Abeer M. El-Naggar, Ibrahim M. Ibrahim, Eslam B. Elkaeed, Ahmed M. Metwaly, Ibrahim H. Eissa
Summary: Fifteen derivatives of quinazoline were synthesized as DNA intercalators, and their cytotoxicity against HCT-116 and HepG2 cancer cell lines as well as their inhibitory effect on Topo II were evaluated. Compound 16 exhibited the highest cytotoxicity and Topo II inhibition, but had low cytotoxicity against Vero cells. Compounds 16, 17, and 18 showed significant DNA binding affinities. Compound 16 also displayed Topo II catalytic inhibitory effect at a concentration of 10 mu M. Further investigations revealed that compound 16 induced apoptosis in HCT-116 cells and arrested growth at the S and G2/M phases, accompanied by increased BAX level and decreased Bcl-2 level compared to control cells. In silico studies demonstrated the ability of the synthesized derivatives to bind to the DNA-Topo II complex.
Article
Chemistry, Medicinal
Xiaohong Yang, Zhi-Peng Wang, Sichuan Xiang, Daoqiang Wang, Yi Zhao, Dong Luo, Yanfei Qiu, Chao Huang, Jian Guo, Yuanwei Dai, Shao-Lin Zhang, Yun He
Summary: A library of novel CAA analogues was synthesized, among which compound F16 exhibited superior water solubility and antiproliferative activities compared to CAA. Mechanism studies confirmed that F16 acted as a dual Topo I and II poison and displayed potent antiproliferative activities against high Topo I and II expression cell lines. In xenograft models, F16 reduced tumor growth without apparent effect on mouse weight, making it a promising lead for the development of novel dual Topo I and II antitumor agents.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
M. Shaheer Malik, Syed Farooq Adil, Ziad Moussa, Hatem M. Altass, Ismail I. Althagafi, Moataz Morad, Mohammad Azam Ansari, Qazi Mohammad Sajid Jamal, Rami J. Obaid, Abdulrahman A. Al-Warthan, Thokhir B. Shaik, Saleh A. Ahmed
Summary: This study describes the rational design and synthesis of two novel bis-naphthalimides with potential DNA interactive properties, using molecular modeling assistance. The compounds showed excellent results in terms of DNA thermal denaturation and cytotoxicity, and two promising molecules were identified for further development.
FRONTIERS IN CHEMISTRY
(2021)
Review
Chemistry, Inorganic & Nuclear
Jean-Francois Longevial, Clemence Rose, Ludivine Poyac, Sebastien Clement, Sebastien Richeter
Summary: This review discusses the importance of porphyrins and N-heterocyclic carbenes in coordination and organometallic chemistry, highlighting their wide applications in metal complexes and catalysis, and specifically describing structural diversity, electronic interplay, and relevant applications in catalysis and biomedicine.
EUROPEAN JOURNAL OF INORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Ahmed I. Khodair, Fatimah M. Alzahrani, Mohamed K. Awad, Siham A. Al-Issa, Ghaferah H. Al-Hazmi, Mohamed S. Nafie
Summary: In this study, various 5-arylidene rhodanine derivatives were synthesized and screened for cytotoxicity against cancer cells, with investigation of the molecular target and cell death mechanism. Compound 6 exhibited potent cytotoxicity and could induce apoptosis by inhibiting topoisomerase II and DNA intercalation. Glucosylated rhodanines may serve as promising drug candidates against cancer.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Tanja V. Soldatovic, Biljana Smit, Emina M. Mrkalic, Sanja Lj. Matic, Ratomir M. Jelic, Marina Cendic Serafinovic, Nevenka Gligorijevic, Milena Cavic, Sandra Arandelovic, Sanja Grguric-Sipka
Summary: Novel Pt-Zn complexes were synthesized and characterized. The complexes showed strong binding to DNA through groove binding, hydrogen bonds, and hydrophobic or electrostatic interaction. Among them, C2 exhibited highly selective cytotoxicity and induced cell cycle arrest and expression of apoptotic related genes.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2023)
Article
Biochemical Research Methods
Quanjuan Zhang, Na Zhang, Yi-Tao Long, Xuhong Qian, Youjun Yang
BIOCONJUGATE CHEMISTRY
(2016)
Article
Chemistry, Analytical
Ziqian Zhang, Jiayao Wu, Zhihao Shang, Chao Wang, Jiagao Cheng, Xuhong Qian, Yi Xiao, Zhiping Xu, Youjun Yang
ANALYTICAL CHEMISTRY
(2016)
Article
Chemistry, Organic
Lei Zhang, Zhisong Huang, Dongdong Dai, Yansheng Xiao, Kecheng Lei, Shaoying Tan, Jiagao Cheng, Yufang Xu, Jianwen Liu, Xuhong Qian
Article
Biochemistry & Molecular Biology
Wenlin Song, Shiliang Li, Yi Tong, Jiawei Wang, Lina Quan, Zhuo Chen, Zhenjiang Zhao, Yufang Xu, Lili Zhu, Xuhong Qian, Honglin Li
Article
Biochemistry & Molecular Biology
Kang Chang, Yanxia Shi, Jianqin Chen, Zenghui He, Zheng Xu, Zhenjiang Zhao, Weiping Zhu, Honglin Li, Yufang Xu, Baoju Li, Xuhong Qian
Article
Biochemistry & Molecular Biology
Lei Zhang, Kecheng Lei, Jingwen Zhang, Wenlin Song, Yuanhong Zheng, Shaoying Tan, Yuwei Gao, Yufang Xu, Jianwen Liu, Xuhong Qian
Article
Chemistry, Multidisciplinary
Jingwen Zhang, Chao Wang, Lei Zhang, Huijing Wu, Yi Xiao, Yufang Xu, Xuhong Qian, Weiping Zhu
Article
Chemistry, Multidisciplinary
Mengfang Tang, Luling Wu, Dan Wu, Chusen Huang, Weiping Zhu, Yufang Xu, Xuhong Qian
Article
Chemistry, Multidisciplinary
Mingwei Zhou, Ke En, Yimin Hu, Yufang Xu, Hong C. Shen, Xuhong Qian
Review
Chemistry, Multidisciplinary
Junlong Zhu, Peipei Jia, Nuo Li, Shaoying Tan, Junhai Huang, Lin Xu
CHINESE CHEMICAL LETTERS
(2018)
Review
Chemistry, Multidisciplinary
Qinghui Ling, Tanyu Cheng, Shaoying Tan, Junhai Huang, Lin Xu
CHINESE CHEMICAL LETTERS
(2020)
Article
Chemistry, Multidisciplinary
Caiyue Wang, Shuping Zhang, Junhai Huang, Lei Cui, Jin Hu, Shaoying Tan
Article
Chemistry, Multidisciplinary
Kang Chang, Jian-Qin Chen, Yan-Xia Shi, Mei-Jian Sun, Peng-Fei Li, Zhen-Jiang Zhao, Wei-Ping Zhu, Hong-Lin Li, Yu-Fang Xu, Bao-Ju Li, Xu-Hong Qian
CHINESE CHEMICAL LETTERS
(2017)
Article
Chemistry, Multidisciplinary
Zuhai Lei, Xinran Li, Xiao Luo, Haihong He, Jing Zheng, Xuhong Qian, Youjun Yang
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2017)
Article
Chemistry, Applied
Dandan Li, Yuqiong Xu, Nannan Zhou, Jianxu Liu, Rui Wang, Tao Cheng, Yun Tang, Weiping Zhu, Yufang Xu, Xuhong Qian
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)