Article
Chemistry, Medicinal
Mingfeng Yu, Theodosia Teo, Yuchao Yang, Manjun Li, Yi Long, Stephen Philip, Benjamin Noll, Gary K. Heinemann, Sarah Diab, Preethi Eldi, Laychiluh Mekonnen, Abel T. Anshabo, Muhammed H. Rahaman, Robert Milne, John D. Hayball, Shudong Wang
Summary: CDK8 plays a crucial role in transcriptional regulation and its dysregulation is associated with various types of cancer. Inhibition of CDK8 with compound 38 showed potent anti-proliferative effects on acute myeloid leukaemia cells without systemic toxicity in preclinical studies. Further research on compound 38 as an anticancer agent is warranted.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Yu Zhao, Chin-Ho Chen, Susan L. Morris-Natschke, Kuo-Hsiung Lee
Summary: By modifying betulinic acid, bevirimat was developed as the first-in-class HIV maturation inhibitor, and further modifications led to the synthesis of compounds with improved activity against wild-type and resistant HIV-1 strains. These derivatives offer expanded structural diversity and chemical space, potentially enhancing antiviral activity and addressing the growing resistance crisis.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Michiko Jo, Keiichi Koizumi, Mizuho Suzuki, Daisuke Kanayama, Yurie Watanabe, Hiroaki Gouda, Hisashi Mori, Mineyuki Mizuguchi, Takayuki Obita, Yuko Nabeshima, Naoki Toyooka, Takuya Okada
Summary: This study aimed to identify GLS1 inhibitors through in silico screening and synthesis. Two compounds were found to exhibit equal potency as known inhibitors, which can contribute to the development of novel GLS1 inhibitors.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Biochemistry & Molecular Biology
Tingjunhong Ni, Fei Xie, Liping Li, Yumeng Hao, Xiaochen Chi, Lan Yan, Dazhi Zhang, Yuanying Jiang, Quanzhen Lv
Summary: Compound 16g, identified from a compound library, showed promising antifungal activity against Candida albicans, including fluconazole-resistant strains. It was found that the compound's ability to disrupt the cell wall of C. albicans contributed to its antifungal activity. Compound 16g has the potential to be further investigated as a lead compound.
Article
Biochemistry & Molecular Biology
Deblina Roy, Mohammad Anas, Ashan Manhas, Satyen Saha, Niti Kumar, Gautam Panda
Summary: In this study, a series of quinoline-imidazole hybrid compounds were synthesized and evaluated for their blood-stage antimalarial activity against Plasmodium falciparum. The results showed that one of the compounds exhibited significant antimalarial efficacy with low cytotoxicity and high selectivity. Furthermore, the study revealed the influence of substituents on the quinoline ring and the role of stereochemistry in the inhibitory activity.
BIOORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Yongtao Li, Renle Du, Yongwei Nie, Tianqi Wang, Yakun Ma, Yan Fan
Summary: The synthesized compound 18i exhibited potent inhibitory activity against CDK4, showing promising anticancer effects in both in vitro and in vivo experiments, especially against breast cancer.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Wenhong Su, Zhiwen Chen, Meiying Liu, Rui He, Chaoyi Liu, Rui Li, Mingshan Gao, Mingyue Zheng, Zhengchao Tu, Zhang Zhang, Tianfeng Xu
Summary: This study presents a new series of JAK3 covalent inhibitors and identifies compound 10f as the most potent inhibitor with high selectivity and inhibitory activity against JAK3. It may serve as a promising tool molecule for treating cancers with aberrantly activated JAK3.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Medicinal
Zhanhui Li, Yongjin Hao, Chengkui Yang, Qing Yang, Shuwei Wu, Haikuo Ma, Sheng Tian, Haohao Lu, Jingrui Wang, Tao Yang, Sudan He, Xiaohu Zhang
Summary: This study reports a series of potent RIPK1 inhibitors, with compound 70 being highly active and stable in blocking necroptosis in inflammatory signaling and cell death. Compound 70 exhibits excellent properties and activity in both in vitro and in vivo experiments.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Keiji Nishiwaki, Shinya Nakamura, Kenji Yoshioka, Eri Nakagawa, Shiori Nakatani, Masato Tsuyuguchi, Takayoshi Kinoshita, Isao Nakanishi
Summary: In this study, new candidate CK2α inhibitors with purine scaffolds were designed and identified using a solvent dipole ordering-based method for virtual screening. The importance of specific groups at different positions on the purine scaffold was supported by virtual docking experiments and experimental structure-activity relationship studies. The results successfully predicted the binding mode of a strong small molecule inhibitor for CK2α and these findings are expected to inspire the development of new CK2α inhibitors with unique binding modes.
CHEMICAL & PHARMACEUTICAL BULLETIN
(2023)
Article
Agriculture, Multidisciplinary
Yu Zhang, Yuming Chen, Xiwei Xun, Shilin Chen, Yuxiu Liu, Qingmin Wang
Summary: A series of 2,4-diphenyl-1,3-oxazolines containing an ether moiety at the para position of the 4-phenyl group were synthesized and tested for acaricidal and insecticidal activity. The results showed that most of the compounds exhibited excellent acaricidal activity against both the larvae and the eggs of Tetranychus cinnabarinus, and some compounds also showed insecticidal activity against other pests. Compound Ic, in particular, showed superior activity compared to the commercial acaricide etoxazole, indicating its potential as a low-cost acaricide agent.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Huijun Ma, Anran Qian, Yazhou Zheng, Xin Meng, Ting Wang, Yinyong Zhang, Lulu Sun, Feng Zou, Bomei Zhao, Shuhua Zhang, Dan Zhang, Yushe Yang
Summary: This article investigates the modification of Amphotericin B to improve its therapeutic properties by suppressing self-aggregation. The modified compound 36 exhibits a stronger antifungal efficacy compared to the current optimal derivative, amphamide, with lower self-aggregation propensity and toxicity.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Huijun Ma, Anran Qian, Yazhou Zheng, Xin Meng, Ting Wang, Yinyong Zhang, Lulu Sun, Feng Zou, Bomei Zhao, Shuhua Zhang, Dan Zhang, Yushe Yang
Summary: In this study, a bisamidation strategy was applied to improve the therapeutic properties of Amphotericin B (AMB) by suppressing self-aggregation. Modifying the basic amino groups at the C16 amide residue enhanced the activity, while introducing lipophilic fragments reduced toxicity. N-methyl-amino acetyl and amino acetyl moieties at the C3' amide helped maintain fungistatic effectiveness. The modified compound 36 exhibited stronger antifungal efficacy and lower toxicity, making it a promising candidate for further development as a second-generation polyene antifungal agent.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Jothi Anantharajan, Nithya Baburajendran, Grace Lin, Yong Yao Loh, Weijun Xu, Nur Huda Binte Ahmad, Shuang Liu, Anna E. Jasson, John Wee Liang Kuan, Elizabeth Yihui Ng, Yee Khoon Yeo, Alvin W. Hung, Joma Joy, Jeffrey Hill, Heide L. Ford, Rui Zhao, Thomas H. Keller, CongBao Kang
Summary: This study demonstrated that the inhibitor-bound form of EYA2 does not favor binding to Mg2+, essential for its Tyr phosphatase activity, and described the optimization and characterization of allosteric inhibitors. Through synthesis of analogues, potency of inhibitors was improved and structure-activity relationships were elucidated. Co-crystal structures confirmed binding modes of inhibitors, providing insight into molecular interactions and potential for structure-based drug discovery.
Article
Biochemistry & Molecular Biology
Mengdie Gong, Mingyan Tu, Hongxia Sun, Lu Li, Lili Zhu, Honglin Li, Zhenjiang Zhao, Shiliang Li
Summary: This study presents three series of compounds designed and synthesized based on the structure of skepinone-L, a known MAPK14 inhibitor. Among the synthesized compounds, 13a and 13b displayed the best inhibitory activities against MAPK11. The structure-activity relationship (SAR) discussed in detail is constructive in optimizing MAPK11 inhibitors.
Article
Chemistry, Medicinal
Jing Zhang, Yang Yang, Xing-Kai Qian, Pei-Fang Song, Yi-Shu Zhao, Xiao-Qing Guan, Li-Wei Zou, Xiaoze Bao, Hong Wang
Summary: In this study, a novel compound P32 was designed and synthesized as a potent mixed-competitive inhibitor of pancreatic lipase (PL), displaying some selectivity over other known serine hydrolases. Molecular docking study revealed that the inhibitory activity of P32 towards PL could be attributed to specific interactions with the active site of PL.
Article
Chemistry, Physical
E. Proniewicz, A. Tata, E. Ilowska, A. Prahl
Summary: This paper utilizes ATR-FTIR and SEIRA techniques to characterize and analyze the selective adsorption of four peptides in body fluids, drawing specific conclusions on molecule-metal interactions and changes during substrate alteration from silver nanoparticles to gold nanoparticles through curve fitting and SEIRA measurements.
JOURNAL OF PHYSICAL CHEMISTRY B
(2021)
Article
Chemistry, Medicinal
Monika A. Lewandowska-Goch, Anna Kwiatkowska, Kevin Ly, Pauline Navals, Hugo Gagnon, Yves L. Dory, Adam Prahl, Robert Day, Teresa Lepek
Summary: The study aimed to improve the affinity of CF1 by altering its PS position. Results showed that substituting the PS position with small hydrophobic residues or a basic residue can enhance the activity of CF1.
ACS MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Paulina Kosikowska-Adamus, Emilia Sikorska, Dariusz Wyrzykowski, Aleksandra Walewska, Anna Golda, Milena Deptula, Michal Obuchowski, Adam Prahl, Michal Pikula, Adam Lesner
Summary: Antimicrobial peptides have broad-spectrum activity against microorganisms and can neutralize toxins and modulate inflammatory responses. Lipidation can enhance their antimicrobial potential and stability, but may also impact selectivity, solubility, and cytotoxicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Edyta Proniewicz, Grzegorz Burnat, Helena Domin, Izabela Maluch, Marta Makowska, Adam Prahl
Summary: The article discusses the application of alanine-scanning technique combined with various spectroscopic methods to study the role of individual amino acid residues in the adsorption process of a peptide fragment on metal nanoparticles. By analyzing spectral profiles and conducting bioactivity studies, conclusions were drawn on the specific interactions between peptides and metal nanoparticles as well as peptide-G protein-coupled receptors (GPCRs).
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Analytical
Anna Wcislo, Izabela Maluch, Pawel Niedzialkowski, Tadeusz Ossowski, Adam Prahl
Summary: Efficient deposition of biomolecules on the surface is crucial for biosensor construction. This study aims to develop a methodology for quantifying enzyme activity using electrochemical methods, focusing on immobilization of peptide substrate on the surface. The method allows observation of peptide-substrate interaction at low concentrations without the need for fluorescent labels, making it competitive with standard spectrofluorimetric methods.
Article
Engineering, Biomedical
Samuel Babity, Frederic Couture, Estefania V. R. Campos, Sarah Hedtrich, Raphael Hagen, Daniel Fehr, Mathias Bonmarin, Davide Brambilla
Summary: This study proposes a minimally invasive alternative strategy of delivering fluorescent ratiometric sensors to the skin using dissolving polymeric microneedles for real-time monitoring of physiological and pathological parameters. The sensors are capable of detecting reactive oxygen species, and are coupled with a custom-built, multiwavelength portable fluorescence detection system.
ADVANCED HEALTHCARE MATERIALS
(2022)
Article
Microbiology
Samira Soltani, Severine Zirah, Sylvie Rebuffat, Frederic Couture, Yvan Boutin, Eric Biron, Muriel Subirade, Ismail Fliss
Summary: This study assessed the gastrointestinal stability and activity of bacteriocins including microcin J25, pediocin PA-1, bactofencin A, and nisin, and found that they were not toxic to human colorectal adenocarcinoma cells. Pediocin PA-1, bactofencin A, and microcin J25 were also shown to have potential for food or clinical applications due to their gastrointestinal stability and lack of toxicity.
FRONTIERS IN MICROBIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Gary Thomas, Frederic Couture, Anna Kwiatkowska
Summary: This review summarizes important studies on furin inhibitors, which are crucial for combating COVID-19 and may be applied to other diseases dependent on furin.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Samira Soltani, Yvan Boutin, Frederic Couture, Eric Biron, Muriel Subirade, Ismail Fliss
Summary: Some bacteriocins and reuterin can be safely applied topically as sanitizers at recommended concentrations, as they show minimal skin toxicity and sensitization effects.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Nawel Mekdad, Thi Minh Hue Tran, Roxane Desjardins, Anna Kwiatkowska, Frederic Couture, Robert Day
Summary: The targeting of proprotein convertase PACE4 has shown efficacy against androgen-independent prostate cancer, inhibiting cell growth and yielding positive results in xenograft assays. These findings demonstrate that PACE4 is a key target in PCa.
SCIENTIFIC REPORTS
(2022)
Editorial Material
Biochemistry & Molecular Biology
Frederic Couture
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Pauline Navals, Anna Kwiatkowska, Nawel Mekdad, Freideiric Couture, Roxane Desjardins, Robert Day, Yves L. Dory
Summary: The use of cyclodextrins (CDs) as drug carriers has been found to improve the unfavorable characteristics and enhance the stability of the anticancer drug C23.
MOLECULAR PHARMACEUTICS
(2023)
Article
Multidisciplinary Sciences
Amro H. Mohammad, Frederic Couture, Isabelle Gamache, Owen Chen, Wissal El-Assaad, Nelly Abdel-Malak, Anna Kwiatkowska, William Muller, Robert Day, Jose G. Teodoro
Summary: PTEN mutation is common in prostate cancer progression, leading to increased expression and secretion of Prorenin Receptor (PRR) and its soluble form. PRR is essential for V-ATPase activity, which is involved in various cancer-related pathways. PACE4, a proprotein convertase, predominantly cleaves PRR and affects V-ATPase activity and prostate cancer cell growth.
Article
Multidisciplinary Sciences
Frederic Couture, Luojun Wang, Frederik Dufour, Keena Chabot-Maheux, Nadia Ekindi Ndongo, Robert Sabbagh, Robert Day
Summary: PACE4-altCT is strongly overexpressed in prostate cancer and may have potential as a biomarker, as demonstrated by immunohistochemistry and ELISA techniques.
SCIENTIFIC REPORTS
(2022)
Article
Toxicology
Samira Soltani, Frederic Couture, Yvan Boutin, Laila Ben Said, Samuel Cashman-Kadri, Muriel Subirade, Eric Biron, Ismail Fliss
Summary: This study investigated the stability and activity of reuterin in the gastrointestinal tract using in vitro models, finding it can be safely used within a certain concentration range. Further in vivo studies are needed to confirm these findings.
TOXICOLOGY REPORTS
(2021)