Article
Chemistry, Physical
Tianyu Cai, Jiaqing Zhang, Jingjing Deng, Qinman Tian, Ruoqi Zhang, Haokai Geng, Yuedong Liu, Keding Zhong, Liting Wen, Chunxiang Liu, Xun Hu, Yuehui Li, Zhipeng Li, Shipeng Hao, Kai Yang, Huizhong Xu
Summary: DNA alkylating agents, including melphalan, cisplatin, and dacarbazine, were found to induce changes in the mechanical properties of DNA and the activity of DNA enzymes, as revealed by single-molecule optical tweezer experiments. These agents stabilized DNA against shearing forces and increased its overstretching force, but had different effects on the elasticity of DNA, with cisplatin inducing the largest change in persistence length. Furthermore, these agents showed varying effects on the processivity of DNA polymerase, with melphalan and cisplatin significantly reducing activity and dacarbazine showing little effect.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Physical
Pradyumna Mazumdar, Diganta Choudhury
Summary: The thermodynamic and kinetic effects of substituting nitrogen mustards with heterocyclic ring systems on the formation of aziridinium ion were studied using DFT calculations. The observed lowering in activities of heterocyclic substituted nitrogen mustards was attributed to an increase in activation energy barriers. The endothermic reaction steps and increased activation energy barriers were found to be caused by delocalization of the positive charge on the aziridinium into the heterocyclic aromatic ring.
COMPUTATIONAL AND THEORETICAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Frauke Antoni, Guenther Bernhardt
Summary: The substitution of esters in bendamustine compounds with a basic moiety increases cytotoxicity, stability, and is bioisosteric. Introducing this modification to nitrogen mustards resulted in enhanced cytotoxic effects against various cancer cells. The novel cytostatics show promise for analyzing the correlation between cytotoxicity and membrane transport, as well as for cancer treatment.
ARCHIV DER PHARMAZIE
(2021)
Article
Medicine, Research & Experimental
Xiaoling Xie, Wanwen Yang, Wuju Zhang, Yingqi Qiu, Zeyou Qiu, Hao Wang, Yuxing Hu, Yuhua Li, Xuan Zhou, Luyao Li, Zhuanzhuan Chen, Chenbo Zhao, Yao Lu, Keqin Zhang, Eryong Lai, Xiaochun Bai
Summary: This study identifies tegaserod maleate as a potential therapeutic agent for acute myeloid leukemia (AML) by targeting TRPM8. TRPM8 plays a crucial role in leukemogenesis and its inhibition promotes apoptosis in AML cells. The study also reveals that TRPM8 regulates the ERK-CREB/c-Fos signaling axis. Overexpression of TRPM8 is observed in AML patients, suggesting its prognostic value in AML.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Environmental Sciences
Morten Suk, Klaus Kuemmerer
Summary: The study evaluated the biodegradability of the prodrug cyclophosphamide (CPA) and its stable human metabolites in the closed bottle test (CBT). Only the main human metabolite, carboxyphosphamide (CXP), showed some biodegradability. Abiotic degradation via SNi and SN2 reactions was proposed as the main degradation pathway. Several new transformation products were formed, some of which were found to be potentially mutagenic and genotoxic. The results highlight the importance of considering human metabolites and identifying potential degradation products in the environmental fate and risk assessment of pharmaceuticals.
SCIENCE OF THE TOTAL ENVIRONMENT
(2023)
Article
Biochemistry & Molecular Biology
Corina Cheptea, Valeriu Sunel, Ana Cezarina Morosanu, Dan Gheorghe Dimitriu, Mihaela Maria Dulcescu-Oprea, Mihai-Daniel Angheluta, Mihaela Miron, Cristina Delia Nechifor, Dana Ortansa Dorohoi, Razvan Nicolae Malancus
Summary: New di-(beta-chloroethyl)-amides were synthesized from 2-mercaptobenzoxazole derived acids using corresponding pivalic mixed anhydrides and di-(beta-chloroethyl)-amine. Optimization of chemical reactions for di-(beta-chloroethyl)-amines was studied, and quantum chemical analysis was conducted to determine the stable configurations and physico-chemical parameters of N-mustards. Mercaptobenzoxazoles with cytotoxic group substitutions in the side chain exhibit antitumor activity and significant inhibition of Ehrlich Ascites compared to the drug I.O.B.-82, as demonstrated in the study.
Article
Biochemistry & Molecular Biology
Dawid Maliszewski, Agnieszka Wrobel, Beata Kolesinska, Justyna Fraczyk, Danuta Drozdowska
Summary: A series of new analogs of nitrogen mustards containing the 1,3,5-triazine ring substituted with dipeptide residue were synthesized and evaluated for the inhibition of both acetylcholinesterase (AChE) and beta-secretase (BACE1) enzymes. The most active compounds against both AChE and BACE1 were identified as compounds A and 4a, with considerable inhibitory concentrations.
Article
Hematology
Jong Bok Lee, Dilshad H. Khan, Rose Hurren, Mingjing Xu, Yoosu Na, Hyeonjeong Kang, Sara Mirali, Xiaoming Wang, Marcela Gronda, Yulia Jitkova, Neil MacLean, Andrea Arruda, Zoe Alaniz, Marina Y. Konopleva, Michael Andreeff, Mark D. Minden, Li Zhang, Aaron D. Schimmer
Summary: The combination therapy of Venetoclax and azacytidine directly activates T cells, increases reactive oxygen species generation, and enhances cytotoxicity against AML cells. Azacytidine also activates the STING/cGAS pathway, rendering AML cells more susceptible to T cell-mediated cytotoxicity.
Article
Chemistry, Medicinal
Caterina Carraro, Tim Helbing, Alexander Francke, Ivonne Zuravka, Alice Sosic, Michele De Franco, Valentina Gandin, Barbara Gatto, D. Richard Gottlich
Summary: The study showed that the new class of nitrogen mustard-based alkylating agent, B-CePs, demonstrated a remarkable selectivity for BxPC-3 pancreatic tumor cells when bearing aromatic moieties embedded in the linker. However, bis-3-chloropiperidines with esters substituted by aliphatic groups or by efficient DNA-interacting groups were potent but nonselective cytotoxic agents. The critical balance between water stability and DNA reactivity was also found to affect the properties of bis-3-chloropiperidines.
Article
Chemistry, Medicinal
Ranran Zhang, Pengyu Wang, Bingyan Wei, Liang Chen, Xiaomin Song, Yihui Pan, Jiahui Li, Jianhua Gan, Tao Zhang, Cai-Guang Yang
Summary: A compound called ZG36 has been found to improve the thermal stability of ClpP in acute myeloid leukemia (AML) cells by directly binding to it. This compound degrades respiratory chain complexes, decreases mitochondrial DNA, and ultimately leads to the collapse of mitochondrial function and death of leukemic cells. In experiments using xenografted mice, ZG36 was also shown to inhibit 3D cell growth and suppress tumorigenesis of AML cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Haley E. Ramsey, Dalton Greenwood, Susu Zhang, Merrida Childress, Maria P. Arrate, Agnieszka E. Gorska, Londa Fuller, Yue Zhao, Kristy Stengel, Melissa A. Fischer, Matthew C. Stubbs, Phillip C. C. Liu, Kelli Boyd, Jeffrey C. Rathmell, Scott W. Hiebert, Michael R. Savona
Summary: The study shows that the novel BET inhibitor INCB054329 in combination with venetoclax can reduce AML burden without inducing toxicity, suggesting a potentially more efficacious treatment option for patients with AML.
CLINICAL CANCER RESEARCH
(2021)
Article
Chemistry, Inorganic & Nuclear
Marlene Mathuber, Michael Gutmann, Mery La Franca, Petra Vician, Anna Laemmerer, Patrick Moser, Bernhard K. Keppler, Walter Berger, Christian R. Kowol
Summary: Receptor tyrosine kinase inhibitors have limitations in cancer therapy due to rapid resistance development and severe adverse effects. Researchers have synthesized cobalt(iii) complexes as hypoxia-activatable prodrugs of the clinically approved tyrosine kinase inhibitor ponatinib, showing promising in vivo anticancer activity in BCR-ABL and FGFR-driven cancer models.
INORGANIC CHEMISTRY FRONTIERS
(2021)
Article
Medicine, Research & Experimental
Shihui Mao, Qing Ling, Jiajia Pan, Fenglin Li, Shujuan Huang, Wenle Ye, Wenwen Wei, Xiangjie Lin, Yu Qian, Yungui Wang, Xin Huang, Jiansong Huang, Jinghan Wang, Jie Jin
Summary: This study found that high expression of CPT1a in AML patients predicts poor clinical outcome, with downregulation of CPT1a inhibiting cell proliferation. Combining the CPT1a inhibitor ST1326 with Bcl-2 inhibitor ABT199 showed strong synergistic inhibitory effects on AML, suggesting a potential new treatment strategy for the disease.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Article
Hematology
Giulia Pianigiani, Andrea Gagliardi, Federica Mezzasoma, Francesca Rocchio, Valentina Tini, Barbara Bigerna, Paolo Sportoletti, Simona Caruso, Andrea Marra, Sara Peruzzi, Eleonora Petito, Giulio Spinozzi, Sharon Shacham, Yosef Landesman, Concetta Quintarelli, Paolo Gresele, Franco Locatelli, Lorenzo Brunetti, Maria Paola Martelli, Brunangelo Falini
Summary: NPM1 is the most frequently mutated gene in adults with acute myeloid leukemia (AML). The interaction between mutant NPM1 (NPM1c) and exportin-1 (XPO1) causes aberrant cytoplasmic dislocation of NPM1c and promotes high expression of homeobox (HOX) genes. However, the current dosing frequency and efficacy of drugs against NPM1-mutated AML are limited. The second-generation XPO1 inhibitor eltanexor, with a higher dosing frequency, can induce sustained downregulation of HOX genes, induce terminal AML differentiation, and prolong the survival of patients, providing important information for the design of clinical trials.
Article
Chemistry, Medicinal
Hamza Mechchate, Regiane Costa de Oliveira, Imane Es-safi, Emmily Myrella Vasconcelos Mourao, Mohamed Bouhrim, Andrii Kyrylchuk, Gemilson Soares Pontes, Dalila Bousta, Andriy Grafov
Summary: This study evaluated the antileukemic activity of a polyphenolic extract from coriander seeds on leukemia cell lines. The extract showed significant antitumoral activity mainly mediated by flavonoids, catechins, and rutin, which exhibited high binding affinity for targeted receptors. This research provides a promising compound for further exploration by research-oriented biopharmacists.
Article
Biochemistry & Molecular Biology
Nikolaos N. Louros, Paraskevi L. Tsiolaki, Aikaterini A. Zompra, Eleni V. Pappa, Vassiliki Magafa, George Pairas, Paul Cordopatis, Christina Cheimonidou, Ioannis P. Trougakos, Vassiliki A. Iconomidou, Stavros J. Hamodrakas
Article
Chemistry, Organic
Vassiliki Psarra, Manolis A. Fousteris, Lothar Hennig, Marina Bantzi, Athanassios Giannis, Sotiris S. Nikolaropoulos
Article
Chemistry, Multidisciplinary
George N. Pairas, Petros G. Tsoungas
Article
Chemistry, Organic
Aggeliki Roumana, Aybike Yektaoglu, Dimanthi Pliatsika, Marina Bantzi, Sotiris S. Nikolaropoulos, Athanassios Giannis, Manolis A. Fousteris
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2018)
Article
Multidisciplinary Sciences
Evgenia Lampropoulou, Ioanna Logoviti, Marina Koutsioumpa, Maria Hatziapostolou, Christos Polytarchou, Spyros S. Skandalis, Ulf Hellman, Manolis Fousteris, Sotirios Nikolaropoulos, Efrosini Choleva, Margarita Lamprou, Angeliki Skoura, Vasileios Megalooikonomou, Evangelia Papadimitriou
SCIENTIFIC REPORTS
(2018)
Article
Biochemistry & Molecular Biology
Dionysios J. Vourtsis, Christos T. Chasapis, George Pairas, Detlef Bentrop, Georgios A. Spyroulias
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2014)
Article
Biochemistry & Molecular Biology
Konstantis F. Konidaris, Georgios A. Dalkas, Eugenia Katsoulakou, George Pairas, Catherine P. Raptopoulou, Fotini N. Lamari, Georgios A. Spyroulias, Evy Manessi-Zoupa
JOURNAL OF INORGANIC BIOCHEMISTRY
(2014)
Article
Biotechnology & Applied Microbiology
C. Mourelatos, S. Nikolaropoulos, M. Fousteris, G. Pairas, M. Argyraki, D. Lykidis, S. Fidani, D. Mourelatos, Th. Lialiaris
MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
(2014)
Article
Health Care Sciences & Services
Vassilis Goulas, Alexandra Kouraklis-Symeonidis, Kyriaki Manousou, Vassileios Lazaris, George Pairas, Paraskevi Katsaouni, Eugenia Verigou, Vassiliki Labropoulou, Vassiliki Pesli, Panagiotis Kaiafas, Urania Papageorgiou, Argiris Symeonidis
Summary: The study found that TDT patients prefer oral ICT and are more satisfied with the burden of deferasirox-containing ICT, even though patients receiving parenteral ICT are more satisfied with the effectiveness of their treatment. There were no significant differences in HRQoL between patients receiving parenteral versus oral ICT.
QUALITY OF LIFE RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Antonios S. Letis, Ean-Jeong Seo, Sotiris S. Nikolaropoulos, Thomas Efferth, Athanassios Giannis, Manolis A. Fousteris
BIOORGANIC & MEDICINAL CHEMISTRY
(2017)
Review
Chemistry, Medicinal
George N. Pairas, Fereniki Perperopoulou, Petros G. Tsoungas, George Varvounis
Meeting Abstract
Biochemistry & Molecular Biology
E. V. Pappa, A. A. Zompra, N. Georgakis, G. Pairas, F. Lamari, P. Tsoungas, N. Labrou, Y. Clonis, P. Cordopatis
JOURNAL OF PEPTIDE SCIENCE
(2014)
Meeting Abstract
Biochemistry & Molecular Biology
N. N. Louros, P. L. Tsiolaki, A. A. Zompra, V. Pappa, V. Magafa, G. Pairas, V. A. Iconomidou, P. Cordopatis, S. J. Hamodrakas
JOURNAL OF PEPTIDE SCIENCE
(2014)
Meeting Abstract
Biochemistry & Molecular Biology
N. Georgakis, E. V. Pappa, A. A. Zompra, G. Pairas, F. Lamari, P. Tsoungas, N. Labrou, P. Cordopatis, Y. Clonis
JOURNAL OF PEPTIDE SCIENCE
(2014)
