Article
Biochemistry & Molecular Biology
Arno Kirchhain, Asta Zubriene, Visvaldas Kairys, Federico Vivaldi, Andrea Bonini, Denise Biagini, Delio Santalucia, Daumantas Matulis, Fabio Di Francesco
Summary: Matrix metalloproteinases play a crucial role in cancer progression and metastasis, and molecular probes have been successfully used to study their activity. In this study, a series of MMP-2 and MMP-9 binding probes were synthesized, showing high selectivity against MMP-2 and potential for sensor fabrication. The experimental results were confirmed by molecular modeling, indicating the potential application of these probes for targeted enzyme detection.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Kavuri Rupa, Dongari Yadagiri, Ratnam Bagavathi, Pazhamalai Anbarasan
Summary: An efficient rhodium-catalyzed synthesis of dihydro-3,1-benzoxazine derivatives has been achieved from aniline derived 1,3-amino alcohols and N-sulfonyl-1,2,3-triazole. This reaction demonstrates the new reactivity of azavinyl carbenes and allows the synthesis of diverse substituted dihydro-3,1-benzoxazines in good yields. Furthermore, the reaction can be extended to diols and used for selective protection of amino alcohols using N-sulfonyl-1,2,3-triazole as the protecting reagent.
Article
Chemistry, Physical
Ab Majeed Ganai, Tabasum Khan Pathan, Sachin Balaso Mohite, Veronika Vojackova, Eva Reznickova, Karolina Kozlanska, Vladimir Krystof, Katya Govender, Sithabile Mokoena, Srinivas Reddy Merugu, Mahesh Palkar, Kimeshni Moodley, Rajshekhar Karpoormath
Summary: A series of novel 1,2,4-triazolo[4,3-b]pyridazine derivatives were designed and synthesized, with good to moderate yields. Spectroscopic studies (NMR and IR) confirmed the synthesis of the compounds, and the fluorine coupled 13C NMR data were explained. The compounds were tested for their in-vitro anti-proliferative activity against four human cancer cell lines, with compound 8l showing the most promising results.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Chemistry, Organic
Pei Dong, Long Chen, Zhendong Yang, Shunxi Dong, Xiaoming Feng
Summary: In this study, an asymmetric catalytic tandem cycloisomerization/[3 + 2] cycloaddition was achieved by a combined system of Au(i) and a chiral N,N'-dioxide-Dy(iii) complex, resulting in various enantioenriched 3H-spiroisobenzofuran-1,3'-pyrrolidine derivatives with moderate to good yields and high diastereo- and enantioselectivities. Possible working modes were proposed to understand the origin of chiral control based on control experiments and the absolute configuration of the product.
ORGANIC CHEMISTRY FRONTIERS
(2021)
Article
Chemistry, Multidisciplinary
Xin Chang, Xiang Cheng, Chun-Jiang Wang
Summary: This article introduces an efficient method for synthesizing pharmaceutical compounds with deuterium labels, which addresses the challenge of building deuterium-containing stereogenic centers in organic synthesis. By combining H/D exchange and 1,3-dipolar cycloaddition in a catalytic asymmetric strategy, bioactive alpha-deuterated pyrrolidine derivatives were constructed with high yields and excellent stereoselectivities.
Article
Chemistry, Organic
Chaolei Liu, Zheng Liang, Ayisenbati Jialingbieke, Jian Gao, Ding Du
Summary: A novel method for the facile assembly of alpha-sulfonyl ketones through N-heterocyclic carbene (NHC)-catalyzed radical-mediated sulfonyl methylation of aldehydes has been developed. The reaction involves single-electron transfer reduction of alpha-iodosulfones by NHC-bound Breslow intermediates, followed by radical-radical coupling to form the target compounds. Furthermore, the catalytic system is also effective for the difunctionalization of styrenes and 1,3-enynes via a three-component radical relay process.
Article
Chemistry, Organic
Twinkle I. Patel, Ramkrishna Laha, Matthew J. Moschitto
Summary: In this study, a selective method for the synthesis of C2-substituted sulfones using sodium tert-butyldimethyl silyloxymethylsulfinate and quinoline N-oxides was reported. This scalable transformation has broad applicability to various quinoline and isoquinoline functionalities.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Lige Liu, Hu Wu, Yan Long, Xinlong Yang, Chuanbiao Du, Yajie Xu, Qinggang Ji
Summary: A series of spiro[pyrrolidine-2,3'-quinoline]-2'-one derivatives were designed and synthesized for the discovery of novel antifungal drugs. These compounds showed inhibitory effects against chitin synthase, excellent antifungal activity, and potency against drug-resistant fungal variants.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Wuchen Xie, Siyu Yang, Li Liang, Meng Wang, Wen Zuo, Yan Lei, Yanmin Zhang, Weifang Tang, Tao Lu, Yadong Chen, Yulei Jiang
Summary: The study describes the discovery of a series of reversible FGFR inhibitors, particularly targeting the acquired resistance caused by GK mutations. Compound 19 exhibits potent in vitro FGFR inhibition, high bioavailability, and an acceptable half-life, making it a potential candidate for overcoming GK mutations in hepatocellular carcinoma treatment.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Yali Wang, Jian Xiao, Aiguo Meng, Chunyan Liu
Summary: This article summarizes the synthetic approaches and applications of multivalent pyrrolidine clusters as glycosidase inhibitors. The multivalent pyrrolidine iminosugars show great potential for the treatment of various diseases by interfering with important biological processes.
Article
Chemistry, Medicinal
Wuchen Xie, Siyu Yang, Li Liang, Meng Wang, Wen Zuo, Yan Lei, Yanmin Zhang, Weifang Tang, Tao Lu, Yadong Chen, Yulei Jiang
Summary: In this study, a reversible FGFR inhibitor was developed for hepatocellular carcinoma, particularly for GK mutations. The compound exhibited potent in vitro inhibition and antitumor activity, and showed tolerance to GK mutations.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Sodeeq Aderotimi Salami, Vincent J. Smith, Rui Werner Macedo Krause
Summary: Spirocyclic compounds, which are found in many active compounds, can be synthesized efficiently and yield high results through the Michael condensation of 3-dicyanomethylene-2H-indol-2-ones with isothiocyanate derivatives under aqueous and mechanochemical conditions. This novel protocol offers advantages such as solvent-free reactions, ambient temperature, short reaction times, experimental simplicity, and excellent yields, making it a suitable alternative to volatile organic solvents.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Organic
Nilesh M. Kahar, Pankaj P. Jadhav, Sudam G. Dawande
Summary: Here, we disclose an efficient and convenient method catalyzed by rhodium(ii) for the synthesis of 2-aminoquinoline derivatives from 2-quinolones and N-sulfonyl-1,2,3-triazoles. This method provides rapid access to 2-aminoquinolines with moderate to excellent yields, and the reaction proceeds through quinolone-hydroxyquinoline tautomerization/O-H insertion to a rhodium(ii)-aza vinyl carbene intermediate generated by denitrogenation of the triazole.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Chemistry, Organic
Min Liu, Wenjian Tang, Hua-Li Qin
Summary: A new sulfonyl fluoride reagent (E)-2-methoxye-thene-1-sulfonyl fluoride (MeO-ESF) was developed and successfully applied for the construction of enaminyl sulfonyl fluoride (N-ESF). This protocol provides a highly atom-economical access to diverse N-ESF and produces CH3OH as the sole byproduct under mild and environmentally benign conditions.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Huan Xiong, Jianping Wu, Hua-Li Qin
Summary: This article presents a method for the construction of indolizine-based heterocyclic sulfonyl fluorides through [3 + 2] cycloaddition reaction. The method features mild conditions, high efficiency, easily obtained starting materials, and a broad substrate scope, which holds great potential value in medicinal chemistry and other related disciplines.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Review
Chemistry, Medicinal
Yongzhen Guo, Xuben Hou, Hao Fang
Summary: Benzimidazole, an aromatic bicyclic heterocycle, is considered valuable in medicinal chemistry and is found in many marketed drugs and natural products that fight various diseases. This review focuses on the pharmacological applications of these drugs, especially anticancer agents, from 2014 to 2019, showcasing their biological activities at targets.
MINI-REVIEWS IN MEDICINAL CHEMISTRY
(2021)
Article
Medicine, Research & Experimental
Wanzhen Lu, Chan Yang, Xinfeng Xu, Chen Chen, Xuben Hou, Hao Fang, Shuwen Liu
Summary: The synthesized HDAC I inhibitor CC-4a was found to reactivate latent HIV-1 at the protein and gene levels with low cytotoxicity and induced apoptosis in HIV-1 infected cell models. CC-4a also showed a synergistic activation effect with prostratin without triggering global T cell activation and down-regulated the expressions of CCR5 and CD4. Furthermore, CC-4a together with antiviral drugs antagonized HIV-1 without mutual interference by enhancing histone acetylation and activating the NF-kappa B pathway.
Review
Pharmacology & Pharmacy
Meng Liu, Shan Gao, Reham M. Elhassan, Xuben Hou, Hao Fang
Summary: SHP2, encoded by PTPN11, is widely recognized as a carcinogenic phosphatase and a promising anti-cancer drug target. It regulates multiple signaling pathways and immune cell function, and has shown therapeutic potential in overcoming drug resistance in cancer treatment.
ACTA PHARMACEUTICA SINICA B
(2021)
Review
Biochemistry & Molecular Biology
Ling Wang, Xuben Hou, Hao Fang, Xinying Yang
Summary: Fluorescent probes have been widely used as important tools for detecting H2O2 to reflect the physiological and pathological conditions of biological systems, with boronate ester and boronic acid groups serving as sensitive responsive parts in these probes. This review summarizes fluorescent probes based on boronate ester/boronic acid groups reported from 2012 to 2020, and classifies the fluorophores into six categories to elaborate the design strategy and systematic performance comprehensively.
CURRENT MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Tao Liang, Junxin Xue, Zefu Yao, Yang Ye, Xinying Yang, Xuben Hou, Hao Fang
Summary: Compound 71, a new HDAC6 inhibitor, showed superior selectivity and activity, with potential application in cancer therapy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Tao Liang, Jia Li, Yi Zhou, Xuben Hou, Xinying Yang, Hao Fang
Summary: BPFP1 is a new tool for Bcl-2 protein quantification, carcinoma cell visualization, and cell sorting. It can fluorescently label carcinoma cells by binding to overexpressed Bcl-2 protein and distinguish carcinoma cells from normal tissue cells based on the different Bcl-2 protein expression levels.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Chen Chen, Xue Li, Huajun Zhao, Meng Liu, Jintong Du, Jian Zhang, Xinying Yang, Xuben Hou, Hao Fang
Summary: The combined use of a DNA minor groove binder and a histone deacetylase (HDAC) inhibitor has shown a synergistic antiproliferation effect. A new series of benzimidazole-hydroxamate hybrids were designed and synthesized to target both DNA minor groove and HDAC. The most active compounds 9k and 9l not only exhibited improved HDAC inhibitory activities but also showed potent antiproliferation activities against tumor cells. Importantly, these compounds demonstrated good in vivo antitumor efficacies and reshaped the tumor immune microenvironment by promoting antigen presentation, activating T cells, and polarizing tumor-infiltrating macrophages with antitumor activity.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Chemistry, Medicinal
Reham M. Elhassan, Xuben Hou, Hao Fang
Summary: The PTP family plays a crucial role in human diseases, with traditional active-site inhibitors facing limitations. Allosteric modulation has emerged as a promising approach in drug development, leading to a growing interest in novel allosteric PTPs inhibitors in recent years.
MEDICINAL RESEARCH REVIEWS
(2022)
Article
Biochemistry & Molecular Biology
Xiao Liang, Xue Li, Zhiyuan Zhao, Yiming Nie, Zefu Yao, Wandi Ren, Xinying Yang, Xuben Hou, Hao Fang
Summary: In this study, a series of hydantoin derivatives were designed and synthesized as novel Mcl-1 inhibitors. Compound M23 and M24 showed good binding affinities against Mcl-1. Additionally, these compounds exhibited good selectivity and stability.
BIOORGANIC CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Yuanju Zhu, Jay Zhang, Feng Min, Xinying Yang, Li Li, Yan Zhang, Xuben Hou, Hao Fang
Summary: The farnesoid X receptor (FXR) is a bile acid activated transcription factor and is involved in important metabolic processes. It is considered a promising therapeutic target for nonalcoholic steatohepatitis (NASH). A series of new FXR agonists were designed in this study, with five compounds showing better activity than the widely used GW4064. The most potent compound S5 also had superior pharmacokinetic profile and in vivo potency compared to the lead compound.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Na Li, Chaobo Li, Juan Zhang, Qian Jiang, Zhaoxue Wang, Shaozhen Nie, Zhenzhen Gao, Guangyao Li, Hao Fang, Shaoda Ren, Xiaojing Li
Summary: Ovarian cancer is characterized by its high mortality rate due to the presence of cancer stem cells, which lead to treatment recurrence and metastasis. A study found that the celastrol derivative 6c showed potential inhibition against ovarian cancer cells and exhibited anti-cancer stem cell effects by inhibiting sphere formation and regulating cell surface markers. Furthermore, compound 6c also attenuated the expression of the STAT3 pathway, suggesting its role in inhibiting ovarian cancer cells.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Chemistry, Multidisciplinary
Yiming Nie, Jia Li, Xinying Yang, Xuben Hou, Hao Fang
Summary: This study used the inhibitory activity of hydroxamic acid against HDACs for QSRR research and employed PCA for dimension reduction of descriptors and GA-BP algorithm for model development. The results showed that incorporating molecular interaction-based features significantly improved the accuracy of the QSRR model.
FRONTIERS IN CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Meng Liu, Shan Gao, Tao Liang, Xueting Qiu, Xinying Yang, Hao Fang, Xuben Hou
Summary: This study observed a synergistic antiproliferation effect of SHP2 inhibitor and HDAC inhibitor and designed a series of SHP2/HDAC dual inhibitors. Compound 8t showed excellent inhibitory activities against SHP2 and HDAC1 and exhibited improved antitumor activities. In addition, compound 8t could trigger antitumor immunity by activating T cells, enhancing antigen presentation, and promoting cytokine secretion.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Xuben Hou, Jintong Du, Hao Fang
Summary: PTPRO may have oncogenic roles in specific cancer types such as pancreatic cancer, blood cancer, and breast cancer. Inhibition of PTPRO can suppress the proliferative abilities of tumor cells, while PTPRO expression promotes immune cell infiltration in pancreatic cancer.
Review
Biochemistry & Molecular Biology
Yunpeng Zhao, Tao Liang, Xuben Hou, Hao Fang
Summary: Histone deacetylation plays crucial roles in chromatin remodeling and gene expression, and aberrant modification can lead to various diseases. HDAC6, a critical member of the HDAC family, serves as a key modulator in many physiological processes, and abnormal expression is linked to cancer, neurodegeneration, and other diseases. Recent advances have been made in the physiological functions, protein structure, and development of HDAC6 selective inhibitors.
CURRENT MEDICINAL CHEMISTRY
(2021)
