Article
Multidisciplinary Sciences
Christine S. Walsh, Mitchell Kamrava, Andre Rogatko, Sungjin Kim, Andrew Li, Ilana Cass, Beth Karlan, Bobbie J. Rimel
Summary: The combination of pembrolizumab, cisplatin and gemcitabine did not show additional benefit beyond chemotherapy alone in patients with recurrent platinum-resistant ovarian cancer. The overall response rate was 60%, with a median progression-free survival of 6.2 months and median overall survival of 11.3 months. However, some patients demonstrated exceptional and durable responses to the treatment.
Article
Biochemistry & Molecular Biology
Moataz A. Shaldam, Hadia Almahli, Andrea Angeli, Rehab Mustafa Badi, Eman F. Khaleel, Abdelrahman I. Zain-Alabdeen, Zainab M. Elsayed, Eslam B. Elkaeed, Rofaida Salem, Claudiu T. Supuran, Wagdy M. Eldehna, Haytham O. Tawfik
Summary: New isatin-based sulphonamides were synthesized as potential dual VEGFR-2 and carbonic anhydrase inhibitors with anticancer activities. The most potent derivatives showed strong VEGFR-2 inhibitory effect but failed to inhibit relevant CA isoforms. Two derivatives were further tested for their impact on cell cycle disturbance and apoptotic potential. Molecular modelling analyses were conducted to assess the binding mode and stability of the target compounds.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Carlos Rodriguez-Nogales, Didier Desmaele, Victor Sebastian, Patrick Couvreur, Maria J. Blanco-Prieto
Summary: A novel bone-affine squalene-based nanomedicine was developed by conjugating a hydroxybisphosphonate moiety to the squalene chain and inserting it into squalenoyl-gemcitabine nanoparticles. The presence of squalenyl-hydroxybisphosphonate enhanced nanoparticles' binding affinity for hydroxyapatite in bones and preserved their anticancer activity in vitro. Further in vivo studies are needed to explore the potential of these nanomedicines for treating bone sarcomas.
Article
Chemistry, Organic
Letian Zhang, Yong Yang, Pengfei Zhang, Chao Chen, Chao Shen
Summary: A practical and mild three-component reaction for the synthesis of various indole derivatives was developed. This method demonstrated high site-selectivity, step economy, and broad substrate scope. The synthetic utility of this approach was demonstrated by the synthesis of N-alkyl triazole compounds via a one-pot two-step click chemistry. Evaluation of the antiproliferative activity of these compounds revealed potent effects against lung adenocarcinoma cells with minimal cytotoxicity to normal cells.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Yangyang Liu, Dongsheng Zhao, Chenghua Zhang, Hui Fang, Qingsitong Shen, Zhixian Wang, Jiangying Cao
Summary: Aminopeptidase N (APN) inhibitors, particularly pyrazoline-based hydroxamate derivatives, have shown significant potential as antitumor agents. Compound 14o exhibited the strongest inhibitory activity against APN, with IC50 value three orders of magnitude better than that of the positive control bestatin. Furthermore, compound 14o demonstrated potent anti-proliferative activities against tumor cells and anti-angiogenic activity.
Article
Chemistry, Multidisciplinary
Heba M. Abosalim, Manal A. Nael, Tarek F. El-Moselhy
Summary: Twenty derivatives of chalcones were synthesized and evaluated for their anticancer activities, with five compounds showing broad antitumor activity against breast and liver cancer cell lines. Compound 3 h exhibited the most powerful anticancer activity and effective inhibition on tubulin, with low toxicity towards normal human cell lines. The docking study revealed that 3 h had the best binding mode among all the derivatives.
Article
Biochemistry & Molecular Biology
Yifei Yang, Pan Chen, Leilei Zhao, Bing Zhang, Changliang Xu, Huibin Zhang, Jinpei Zhou
Summary: BRD4 inhibitor HB100-A7 showed excellent inhibitory activities against BRD4 protein in vitro, suppressing pancreatic cancer cell proliferation and inducing apoptosis. In vivo study further confirmed its significant tumor growth inhibition effect in a pancreatic mouse tumor model, suggesting its potential as a promising lead compound for further development as a new generation of small molecule inhibitors targeting BRD4.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
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, Organic
Amal Homer, Oliver Seitz
Summary: Forced intercalation probes (FIT probes) are nucleic acid probes with a fluorescent dye surrogate nucleobase that enhances fluorescence upon hybridization. We synthesized new fluorogenic base surrogates by introducing nine different derivatives into FIT probes. Substituents at the quinoline and benzothiazole parts of the probes affect fluorescence turn-on and brightness of probe-target duplexes. A tricyclic benzothiazole derivative showed up to 18.6-fold enhancement of fluorescence upon hybridization, making it a superior alternative to thiazole orange in FIT probes.
SYNTHESIS-STUTTGART
(2023)
Article
Chemistry, Multidisciplinary
Yuki Hirose, Kaori Hashiya, Toshikazu Bando, Hiroshi Sugiyama
Summary: The study demonstrated that the conjugation of chlorambucil to cyclic PIPs showed higher DNA alkylation activity and cytotoxicity against prostate cancer cells compared to hairpin PIP-chlorambucil conjugates. The results suggest that the novel cPIP-Chbs could be promising DNA alkylating anticancer drugs.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Saeid Hadi Ali Janvand, Lucy Kate Ladefoged, Asta Zubriene, Andrius Sakalauskas, Gunna Christiansen, Virginija Dudutiene, Birgit Schiott, Daumantas Matulis, Vytautas Smirnovas, Daniel E. Otzen
Summary: Fluorinated sulfonamide compounds can inhibit the formation of amyloid fibrils, potentially providing therapeutic effects against amyloid-related disorders such as Parkinson's, Alzheimer's, and type 2 diabetes, possibly by maintaining insulin in its native monomeric state.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Chemistry, Organic
Sami A. Al-Hussain, Fatimah Alshehrei, Magdi E. A. Zaki, Marwa F. Harras, Thoraya A. Farghaly, Zeinab A. Muhammad
Summary: This research focused on synthesis of novel fluorinated hydrazonoyl halides and their use in generating thiazole derivatives and imidazopyrazole systems. Antimicrobial testing showed varied activity levels among the synthesized compounds, with one derivative showing promising activity against Candida albicans. Docking simulation indicated good binding affinity of several compounds in the ATP binding site of DNA gyrase B enzyme.
JOURNAL OF HETEROCYCLIC CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Wu-Xi Zhou, Chen Chen, Xiao-Qin Liu, Ying Li, Yao-Lan Lin, Xiu-Tao Wu, Ling-Yi Kong, Jian-Guang Luo
Summary: A potential novel GLS1 inhibitor has been developed through synthesis and optimization, showing effective therapeutic effects on triple-negative breast cancer. The inhibitor induces apoptosis in MDA-MB-231 cells by influencing metabolic pathways. Animal model experiments demonstrate significant therapeutic effects of the inhibitor.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Omer Bayazeid, Taufiq Rahman
Summary: The study analyzed the molecular targets of 41 US FDA-approved kinase inhibitors, focusing on 18 tyrosine kinase inhibitors. By evaluating their selectivity profiles and interactions with multiple targets at clinically relevant doses, the research aimed to explore the correlation between target engagement profiles and reported side effects. The findings provide insights into the off-target effects of kinase inhibitors and their impact on toxicity, contributing to a better understanding of the structural-activity relationship of KIs.
Review
Chemistry, Multidisciplinary
Harshita Shet, Rajesh Sahu, Yogesh S. Sanghvi, Anant R. Kapdi
Summary: Fluorinated nucleosides and oligonucleotides are widely used as probes for studying nucleic acid interactions, structures, transformations, and biomedical applications. The unique properties of fluorine atoms, such as small size, electronegativity, lipophilicity, and stereochemical control, have attracted attention for the fluorination of preformed nucleosides and/or nucleotides. This review discusses the synthetic protocols for selective fluorination of sugar or base moieties in preformed nucleosides, nucleotides, and nucleic acids using specific fluorinating reagents.
Article
Biochemistry & Molecular Biology
Mohamed A. Nasr, Galina Dovbeshko, Stephen L. Bearne, Nagwa El-Badri, Cherif F. Matta
Review
Chemistry, Multidisciplinary
Stephen L. Bearne
CHEMISTRY-A EUROPEAN JOURNAL
(2020)
Article
Biochemistry & Molecular Biology
Amar Nath Sharma, Lia Grandinetti, Erin R. Johnson, Martin St Maurice, Stephen L. Bearne
Article
Multidisciplinary Sciences
Johnathon R. Emlaw, Christian J. G. Tessier, Gregory D. McCluskey, Melissa S. McNulty, Yusuf Sheikh, Kelly M. Burkett, Maria Musgaard, Corrie J. B. daCosta
Summary: The study found that a single historical amino acid substitution can influence the assembly of muscle-type acetylcholine receptors, thereby increasing receptor complexity. Through a single amino acid substitution, the research revealed that subunit entrenchment can be driven, providing new insights into the evolution of protein subunit complexity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Colin D. Douglas, Lia Grandinetti, Nicole M. Easton, Oliver P. Kuehm, Joshua A. Hayden, Meghan C. Hamilton, Martin St Maurice, Stephen L. Bearne
Summary: 2-FPBA is shown to be a potent reversible, slow-onset inhibitor of mandelate racemase (MR), forming a benzoxaborole through intramolecular cyclization due to the N-zeta-B dative bond formation between Lys 166 and 2-FPBA. The structure of the resulting product when using o-carbonyl arylboronic acid reagents to modify proteins depends on the protein architecture at the site of modification.
Article
Biochemistry & Molecular Biology
Mitesh Nagar, Joshua A. Hayden, Einat Sagey, George Worthen, Mika Park, Amar Nath Sharma, Christopher M. Fetter, Oliver P. Kuehm, Stephen L. Bearne
Summary: The study demonstrates that the binding determinant on the interdigitating loop can play a significant role in governing substrate specificity and catalysis within the enolase superfamily. Various substitutions at position 93 of the MR enzyme resulted in changes in catalytic efficiency and substrate binding, but did not necessarily lead to the acquisition of new catalytic activities.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2022)
Review
Biochemistry & Molecular Biology
Stephen L. Bearne, Chen-Jun Guo, Ji-Long Liu
Summary: Cytidine-5'-triphosphate synthase (CTPS) is an enzyme involved in the biosynthesis of CTP. It requires an allosteric effector (GTP) to activate the glutamine hydrolysis process and also plays a role in the assembly and maintenance of the NH3 tunnel.
Article
Chemistry, Medicinal
Thomas D. Gillis, Stephen L. Bearne
Summary: Repurposed antiviral drugs have the potential to affect the activity of a critical pyrimidine nucleotide biosynthetic enzyme.
Article
Microbiology
Eric S. Pringle, Brett A. Duguay, Maxwell P. Bui-Marinos, Rory P. Mulloy, Shelby L. Landreth, Krishna Swaroop Desireddy, Stacia M. Dolliver, Shan Ying, Taylor Caddell, Trinity H. Tooley, Patrick D. Slaine, Stephen L. Bearne, Darryl Falzarano, Jennifer A. Corcoran, Denys A. Khaperskyy, Craig McCormick
Summary: Reported the inhibitory effect of thiopurines on the replication of HCoV-OC43 and SARS-CoV-2 coronaviruses, and discovered defective Spike trafficking and processing as a result of 6-TG treatment.
Editorial Material
Biology
Nigel G. J. Richards, Stephen L. Bearne, Yuki Goto, Emily J. Parker
Summary: Physical organic chemistry and mechanistic thinking are instrumental in understanding the chemical processes and metabolic transformations in living organisms. They have also contributed to advancements in the fields of biological function, chemical ecology, and alternative chemistries. The symposium initially planned for December 2020 was postponed due to the COVID-19 pandemic and held as an online event in December 2021. This themed issue showcases research on biosynthetic pathways, enzyme catalysis, genetic alphabets, and alternative chemistries, providing a foundation for understanding the emergence of complex biological systems.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2023)
Article
Chemistry, Organic
Noa T. Sorbara, Joshua W. M. MacMillan, Gregory D. McCluskey, Stephen L. Bearne
ORGANIC & BIOMOLECULAR CHEMISTRY
(2019)
Letter
Chemistry, Multidisciplinary
Stephen L. Bearne
CHEMICAL & ENGINEERING NEWS
(2019)
Article
Chemistry, Organic
Stephen L. Bearne
ORGANIC & BIOMOLECULAR CHEMISTRY
(2019)
Article
Biochemistry & Molecular Biology
Matthew L. Harty, Amar Nath Sharma, Stephen L. Bearne