Article
Biochemistry & Molecular Biology
Heba K. A. El-Mawgoud, Ahmed M. Fouda, Mohammed A. A. El-Nassag, Ahmed A. Elhenawy, Mohammed Y. Alshahrani, Ahmed M. El-Agrody
Summary: A series of novel oxygen-containing heterocyclic linked 1H-benzo[f]chromene moieties were designed and synthesized, showing anti-proliferative activity against cancer cell lines, particularly MCF-7, HCT-116, and HepG-2. The compounds exhibited potential mechanisms involving cell cycle arrest and inhibition of topoisomerase enzymes.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Chemistry, Multidisciplinary
Samia M. M. Al-Muntaser, Ahmed A. A. Al-Karmalawy, Abeer M. M. El-Naggar, Ali Khalil Ali, Nour E. A. Abd El-Sattar, Eslam M. M. Abbass
Summary: In this study, new 4-thiophenyl-pyrazole, pyridine, and pyrimidine derivatives were designed as dual EGFR/VEGFR-2 inhibitors and evaluated for their anticancer and antimicrobial activities. Some of the compounds showed promising anticancer activities and significant dual EGFR/VEGFR-2 inhibition. Additionally, most of the compounds exhibited strong to moderate antibacterial and antifungal effects.
Article
Biochemistry & Molecular Biology
Esraa A. Abdelsalam, Amer Ali Abd El-Hafeez, Wagdy M. Eldehna, Mahmoud A. El Hassab, Hala Mohamed M. Marzouk, Mahmoud M. Elaasser, Nageh A. Abou Taleb, Kamilia M. Amin, Hatem A. Abdel-Aziz, Pradipta Ghosh, Sherif F. Hammad
Summary: A new series of thiazolyl-pyrazoline derivatives were synthesized and evaluated for their inhibitory activities against EGFR and VEGFR-2. Compounds 10b and 10d exhibited potent and selective inhibition towards both receptor tyrosine kinases, as well as demonstrated efficacy against non-small lung cancer cells and EGFR-mutated NSCLC cell lines. These compounds also induced cell cycle arrest, apoptosis, and inhibited migration in A549 cancer cells.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Mostafa M. Ghorab, Aiten M. Soliman, Khaled El-Adl, Noura S. Hanafy
Summary: Here, we synthesized a series of new quinazoline sulfonamide conjugates 2-16 and evaluated their potential as anticancer agents by targeting EGFRT790M and VEGFR-2. The compounds were designed based on the structure requirements of the receptors and confirmed using spectral data. They were tested for cytotoxicity against four cancer cell lines and the most active compound (15) showed significant cytotoxic and inhibitory activity against EGFR and VEGFR.
BIOORGANIC CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Geunho Choi, Daegeun Kim, Junehwan Oh
Summary: This study utilized artificial intelligence to discover potential drugs that can overcome acquired resistance in lung cancer patients, reducing the limitations of the current drug discovery process.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Ibrahim H. Eissa, Reda G. Yousef, Eslam B. Elkaeed, Aisha A. Alsfouk, Dalal Z. Husein, Ibrahim M. Ibrahim, Mohamed S. Alesawy, Hazem Elkady, Ahmed M. Metwaly
Summary: A new semisynthetic derivative has been designed as an antiangiogenic compound targeting EGFR protein. The compound has shown potential binding to EGFR and demonstrated anti-tumor activity.
Article
Biochemistry & Molecular Biology
Eman Z. Elrazaz, Rabah A. T. Serya, Nasser S. M. Ismail, Amgad Albohy, Dalal A. Abou El Ella, Khaled A. M. Abouzid
Summary: The study reports the design, synthesis, and evaluation of a series of 4-substituted thieno[2,3-d]pyrimidine derivatives as VEGFR-2 inhibitors, showing potent inhibitory activities against VEGFR-2. Molecular docking analysis and molecular dynamics simulation were conducted to further investigate the findings, indicating the potential of these compounds as therapeutic agents.
BIOORGANIC CHEMISTRY
(2021)
Review
Pharmacology & Pharmacy
Yazan Haddad, Marek Remes, Vojtech Adam, Zbynek Heger
Summary: The study utilized variations in 110 crystal structures to assemble eight distinct families highlighting the C-helix orientation in the N-lobe of the EGFR kinase domain. These families shared similar mutational profiles, ligand R-groups facing the C-helix, mutation sites, and DFG domain.
DRUG DISCOVERY TODAY
(2021)
Article
Biochemistry & Molecular Biology
Hend A. A. Ezelarab, Taha F. S. Ali, Samar H. Abbas, Ahmed M. Sayed, Eman A. M. Beshr, Heba A. Hassan
Summary: New 3-substituted oxindole derivatives were synthesized and evaluated as antiproliferative agents. Among the tested compounds, compounds 6f and 6g showed remarkable antiproliferative activity against leukemia and breast cancer cell lines. Compound 6f exhibited the most promising antiproliferative activity against MCF-7 (human breast cancer), and inhibited receptor tyrosine EGFR and tubulin polymerization.
MOLECULAR DIVERSITY
(2023)
Article
Medicine, Research & Experimental
Hui Hua, Jiajia Zeng, Haixin Xing, Yuxin He, Linyu Han, Nasha Zhang, Ming Yang
Summary: This study systematically evaluated the role of genetic variants in A-to-I editing genes on the prognosis of NSCLC patients receiving EGFR-TKIs therapy. The researchers identified several SNPs in the ADAR gene that were significantly associated with patient prognosis and found that silencing ADAR enhanced the sensitivity of NSCLC cells to gefitinib. These findings highlight the importance of A-to-I RNA editing in drug resistance and suggest ADAR as a potential therapeutic target for unresectable NSCLC.
Article
Biochemistry & Molecular Biology
Mona H. Ibraheim, Ibrahim Maher, Ibrahim Khater
Summary: The study aims to find novel inhibitors for EGFR and VEGFR-2 kinases through molecular docking, pharmacokinetic analysis, interaction analysis, and molecular dynamic simulation. Compound 2C showed good docking performance, drug-likeness, and interactions, and it can stably bind to the kinases. Therefore, compound 2C may be a promising option to slow the spread of cancer.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Multidisciplinary
Hazem Elkady, Osama A. El-Dardir, Alaa Elwan, Mohammed S. Taghour, Hazem A. Mahdy, Mohammed A. Dahab, Eslam B. Elkaeed, Bshra A. Alsfouk, Ibrahim M. Ibrahim, Dalal Z. Husein, Elsayed E. Hafez, Amira M. G. Darwish, Ahmed M. Metwaly, Ibrahim H. Eissa
Summary: In this study, novel VEGFR-2-targeting thiazolidine-2,4-dione derivatives were designed and synthesized. The compounds demonstrated potent anti-VEGFR-2 activity and inhibited the growth of three different cancer cell types. Compound 15 showed the best anti-VEGFR-2 potency and exhibited remarkable anti-proliferative activities against the tested cancer cell lines. Computational methods were used to analyze the molecular characteristics of the VEGFR-2-15 complex, and ADMET and toxicity experiments were conducted to evaluate the therapeutic potential of the synthesized compounds. The findings suggest that compound 15 may serve as an effective anticancer lead compound.
Article
Chemistry, Medicinal
Mohamed A. Abdelgawad, Arafa Musa, Atiah H. Almalki, Sami Alzarea, Ehab M. Mostafa, Mostafa M. Hegazy, Gomaa Mostafa-Hedeab, Mohammed M. Ghoneim, Della Gt Parambi, Rania B. Bakr, Nayef S. Al-Muaikel, Abdullah S. Alanazi, Metab Alharbi, Waqas Ahmad, Syed Na Bukhari, Mohammad M. Al-Sanea
Summary: In this study, three potential dual EGFR and COX-2 inhibitors were prepared and evaluated, with compounds C4 and G4 showing good inhibitory activity and cytotoxicity against multiple cancer cell lines. Virtual docking study results were consistent with experimental findings, confirming the inhibitory activities of the synthesized compounds for both COX and EGFR.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2021)
Review
Biochemistry & Molecular Biology
Nichole E. M. Kaufman, Simran Dhingra, Seetharama D. Jois, Maria da Graca H. Vicente
Summary: EGFR and VEGFR are frequently overexpressed membrane-bound receptor tyrosine kinase proteins in cancers, making them attractive targets for imaging and therapy. Inhibition modalities commonly used to target these receptors include TKIs, antibodies, and nanobodies. Recent advances in molecular imaging techniques, particularly near-IR fluorescence imaging, show promise for cancer detection and treatment.
Article
Chemistry, Medicinal
Meredith S. Eno, Jason D. Brubaker, John E. Campbell, Chris De Savi, Timothy J. Guzi, Brett D. Williams, Douglas Wilson, Kevin Wilson, Natasja Brooijmans, Joseph Kim, Aysegul Ozen, Emanuele Perola, John Hsieh, Victoria Brown, Kristina Fetalvero, Andrew Garner, Zhuo Zhang, Faith Stevison, Rich Woessner, Jatinder Singh, Yoav Timsit, Caitlin Kinkema, Clare Medendorp, Christopher Lee, Faris Albayya, Alena Zalutskaya, Stefanie Schalm, Thomas A. Dineen
Summary: While EGFR tyrosine kinase inhibitors have revolutionized the treatment of NSCLC, the development of resistance mutations remains a challenge. This study introduces a novel reversible inhibitor, BLU-945, that shows promising activity against different resistance mutations. Clinical trials are currently underway to evaluate its efficacy and safety.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Taiki Morita, Hiroki Murakami, Yasunobu Asawa, Hiroyuki Nakamura
Summary: In this study, a palladium-catalyzed N-H/B-H double activation of 1,2-dihydro-1,2-benzazaborines proceeded via cycloaddition with vinyl ethylene carbonate to produce polycyclic oxazaborolidines in moderate to high yields. Chiral oxazaborolidines were synthesized using a SPINOL-derived phosphoramidite as a chiral ligand, showing excellent enantioselectivity. The resulting oxazaborolidines demonstrated good stability in various carbon-carbon coupling reactions.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Medicine, Research & Experimental
Tae-Hee Han, Min Kyung Park, Hiroyuki Nakamura, Hyun Seung Ban
Summary: Capsaicin inhibits cell growth and HIF activation in lung cancer cells by reducing HIF-1α accumulation through the suppression of mitochondrial respiration. This may potentially offer anticancer therapeutic effects in lung cancer under hypoxic conditions.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Hiroki Ueda, Peter Wipf, Hiroyuki Nakamura
Summary: Chiral sp(3)-rich bicyclo[3.3.1]nonane scaffolds were synthesized as single diastereomers using different types of intramolecular addition reactions. The compound library constructed by changing the chirality of the ligands exhibited concentration-dependent inhibition of HIF-1 transcriptional activity. Compound 16f showed the highest activity and had a distinct mechanism of action compared to known compounds with the common bicyclo[3.3.1]nonane skeleton.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Physical
Keita Nakane, Tatsuya Niwa, Michihiko Tsushima, Shusuke Tomoshige, Hideki Taguchi, Hiroyuki Nakamura, Minoru Ishikawa, Shinichi Sato
Summary: The novel function of BODIPY as a catalyst for chemical labelling of histidine is revealed. It oxidizes histidine residues using singlet oxygen produced by its photosensitizer property, and the oxidized histidine is then trapped by a nucleophile. This selective labelling allows site-selective functionalization of proteins/peptides.
Article
Chemistry, Multidisciplinary
Masato Tsuda, Taiki Morita, Hiroyuki Nakamura
Summary: This paper reports the synthesis of benzoisoxazoloborines via gold(I)-catalyzed propargyl azaClaisen rearrangement and electrophilic borylative cyclization. The in situ generation of aminoisoxazole intermediate with allenyl functionality is crucial for obtaining highly substituted compounds. Furthermore, the N-O bond insertion of a zinc carbenoid was used to synthesize oxazine-fused azaborine.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Michihiko Tsushima, Shinichi Sato, Kazuki Miura, Tatsuya Niwa, Hideki Taguchi, Hiroyuki Nakamura
Summary: Intracellular photocatalytic-proximity labeling (iPPL) is a method used to analyze protein-protein interactions in the microenvironment of living cells. Acriflavine was found to be an efficient cell-membrane-permeable photocatalyst for iPPL experiments. iPPL was applied to study the histone-associated protein H2B in cells, and it was found that proteins interacting directly with histones and RNA-binding proteins could be selectively labeled.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Hiroshi Kitamura, Yuma Otake, Naoto Sugisawa, Hiroki Sugisawa, Tomonori Ida, Hiroyuki Nakamura, Shinichiro Fuse
Summary: In this study, a sequential nucleophilic substitution reaction was demonstrated in a continuous-flow reactor, where the occurrence of over nucleophilic substitution during the reaction was suppressed by the addition of imidazole. The findings suggest that the presence of imidazole significantly improves the selectivity of the reaction.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Analytical
Satoshi Okada, Yuka Muto, Bo Zhu, Hiroshi Ueda, Hiroyuki Nakamura
Summary: Researchers have developed a fluorescent peptide sensor called 26-Dan for the highly sensitive and convenient detection of SARS-CoV-2. This sensor is adaptable to virus variants and, when combined with a portable microfluidic fluorescence polarization analyzer, can detect the virus within 3 minutes. This study represents a promising step towards a rapid and convenient test for SARS-CoV-2 and other potential pandemic-prone diseases.
ANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Inorganic & Nuclear
Antonello Merlino, Takafumi Ueno, Domenico Loreto, Basudev Maity, Taiki Morita, Hiroyuki Nakamura
Summary: Due to their unique coordination structure, dirhodium paddlewheel complexes have attracted interest in various research fields, such as medicinal chemistry and catalysis. Previous studies have focused on conjugating these complexes to proteins and peptides to develop artificial metalloenzymes. However, this work explores the fixation of dirhodium complexes into protein crystals to create heterogeneous catalysts. The results show that these biohybrid materials can be used as effective catalysts for reactions in aqueous solutions.
INORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Sun Hyeok Lee, Chul Soon Park, Kyung Kwan Lee, Tae-Hee Han, Hyun Seung Ban, Chang-Soo Lee
Summary: In this study, novel near-infrared probes were synthesized for fluorescence imaging of NTR activity. NIR-HCy-NO2 1 exhibited superior performance compared to the other two probes in terms of catalytic efficiency and limit of detection. Furthermore, NIR-HCy-NO2 1 was found to react with type I mitochondrial NTR in live cell imaging. NIR-HCy-NO2 demonstrated great potential for various NTR-related applications, including NTR activity imaging in vivo.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Sreenivasulu Godesi, Jeong-Ran Han, Jang-Keun Kim, Dong-Ik Kwak, Joohan Lee, Hossam Nada, Minkyoung Kim, Hyun-A Yang, Joo-Young Im, Hyun Seung Ban, Chang Hoon Lee, Yongseok Choi, Misun Won, Kyeong Lee
Summary: In this study, a series of novel dual MDH1/2 inhibitors were designed and synthesized, and their structure-activity relationship was investigated. Among the tested compounds, compound 50 containing a piperidine ring showed improved growth inhibition of A549 and H460 lung cancer cell lines compared to LW1497. Compound 50 reduced the total ATP content in A549 cells in a dose-dependent manner and suppressed the accumulation of HIF-1a and expression of HIF-1a target genes such as GLUT1 and PDK1. Furthermore, compound 50 inhibited HIF-1a-regulated CD73 expression under hypoxia in A549 lung cancer cells. These results suggest that compound 50 may be a potential candidate for the development of next-generation dual MDH1/2 inhibitors to target lung cancer.
Article
Biochemistry & Molecular Biology
Kazuki Miura, Manjusha Joshi, Taiki Morita, Hiroyuki Nakamura
Summary: This study developed an efficient method for synthesizing bicyclo[3.3.1]nonane, and found that its derivatives can inhibit gene transcription and cell growth. The compounds also showed different mechanism of action compared to conventional HSP90 inhibitors.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Satoshi Okada, Kai Nishimura, Qarri Ainaya, Kouichi Shiraishi, Sergey A. Anufriev, Igor B. Sivaev, Yoshinori Sakurai, Minoru Suzuki, Masayuki Yokoyama, Hiroyuki Nakamura
Summary: In this study, a gadolinium-boron-conjugated albumin (Gd-MID-BSA) was developed for MRI-guided neutron capture therapy. The accumulation of Gd-MID-BSA in tumors was confirmed by MRI and biodistribution analysis. The concentration ratios of boron and gadolinium in tumors satisfied the requirements for boron neutron capture therapy (BNCT) and gadolinium neutron capture therapy (GdNCT). The conjugation of gadolinium and boron in the albumin molecule enhanced the therapeutic effect of BNCT and showed potential as a promising treatment for malignant tumors.
MOLECULAR PHARMACEUTICS
(2023)
Article
Chemistry, Organic
Tomoya Doi, Kohei Umedera, Kazuki Miura, Taiki Morita, Hiroyuki Nakamura
Summary: The sp3-rich bridged diazatricycloundecane scaffold was synthesized via gold(i)-catalysed Conia-ene reaction. The resulting scaffold allowed the construction of a library of sp(3)-rich compounds. Among the synthesized compounds, compounds 6e and 6f inhibited the hypoxia inducible factor 1 (HIF-1) downstream signaling pathway without affecting HIF-1 alpha mRNA expression.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Kohei Umedera, Taiki Morita, Hiroyuki Nakamura
Summary: Asymmetric construction of densely functionalized three-dimensional aza-tetracyclic scaffolds was achieved through intramolecular Diels-Alder reaction of bicyclic precursors derived from l-tyrosine. Three substituents were systematically introduced into the developed scaffolds in various combinations, demonstrating their high utility in drug discovery.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
