Synthesis of Deuterated Endochin ‐Like Quinolones
A prodrug of antimalarial drug candidateELQ-300 is currently in preclinical development, requiring the availability of isotopically labeled analogs. A suitable method for isotopic labeling of these compounds has not yet been reported. Here, we describe a method for the deuteration ofELQ-300 and its prodrug using deuterated acetic acid. ABSTRACTMalaria continues to be a serious and debilitating disease. The emergence and spread of high-level resistance to multiple antimalarial drugs byPlasmodium falciparum has brought about an urgent need for new treatments that will be active against multidrug resistant malaria infections....
Source: Journal of Labelled Compounds and Radiopharmaceuticals - April 26, 2024 Category: Biochemistry Authors: Sovitj Pou,
Rolf W. Winter,
Katherine M. Liebman,
Rosie A. Dodean,
Aaron Nilsen,
Andrea DeBarber,
J. Stone Doggett,
Michael K. Riscoe Tags: RESEARCH ARTICLE Source Type: research
Disrupting the interaction between a p53 gain ‐of‐function mutant and the transcriptional co‐activator PC4 reverses drug resistance in cancer cells
In a tumor cell harboring the gain-of-function mutant R273Hp53, the mutant p53 protein is recruited to the promoters of theMDR1 andUBE2C multidrug resistance-associated genes, assisted by the chromatin-associated protein PC4. This recruitment upregulates both genes. A peptide designed to disrupt the R273Hp53 –PC4 interaction, downregulatesMDR1 andUBE2C expression, sensitizing the cells to doxorubicin. This suggests that the PC4 –R273Hp53 interaction is a promising target for reducing drug resistance. PC4 is a chromatin-associated protein and transcriptional coactivator whose role in gene regulation by wild-type p53 is ...
Source: FEBS Letters - April 26, 2024 Category: Biochemistry Authors: Priya Mondal,
Kumar Singha Roy,
Supriya Varsha Bhagat,
Siddharth Singh,
Anupa Chattopadhyay,
Damayanti Das Ghosh,
Tapas K. Kundu,
Susanta Roychoudhury,
Siddhartha Roy Tags: Research Article Source Type: research
NhaA: A promising adjuvant target for colistin against resistant Escherichia coli
Int J Biol Macromol. 2024 Apr 23:131833. doi: 10.1016/j.ijbiomac.2024.131833. Online ahead of print.ABSTRACTThe emergence and widespread of multidrug-resistant Gram-negative bacteria have posed a severe threat to human health and environmental safety, escalating into a global medical crisis. Utilization of antibiotic adjuvants is a rapid approach to combat bacterial resistance effectively since the development of new antimicrobial agents is a formidable challenge. NhaA, driven by proton motive force, is a crucial secondary transporter on the cytoplasmic membrane of Escherichia coli. We found that 2-Aminoperimidine (2-AP), ...
Source: International Journal of Biological Macromolecules - April 25, 2024 Category: Biochemistry Authors: Xuelin Wang Yong Cui Zhaohui Wang Huilin Jiang Lei Ma Wenwen Li Xinyi Yang Jinghai Zhang Yongshan Zhao Guoqing Li Source Type: research
Inhibition of human drug transporter activities by succinate dehydrogenase inhibitors
Chemosphere. 2024 Apr 23:142122. doi: 10.1016/j.chemosphere.2024.142122. Online ahead of print.ABSTRACTSuccinate dehydrogenase inhibitors (SDHIs) are widely-used fungicides, to which humans are exposed and for which putative health risks are of concern. In order to identify human molecular targets for these environmental chemicals, the interactions of 15 SDHIs with activities of main human drug transporters implicated in pharmacokinetics were investigated in vitro. 5/15 SDHIs, i.e., benzovindiflupyr, bixafen, fluxapyroxad, pydiflumetofen and sedaxane, were found to strongly reduce activity of the renal organic anion transp...
Source: Chemosphere - April 25, 2024 Category: Chemistry Authors: Marie Kerhoas Marc Le V ée Jennifer Carteret Elodie Jouan Valentin Tastet Arnaud Bruy ère Laurence Huc Olivier Fardel Source Type: research
Novel small multidrug resistance protein Tmt endows the Escherichia coli with triphenylmethane dyes bioremediation capability
Biotechnol Lett. 2024 Apr 25. doi: 10.1007/s10529-024-03480-5. Online ahead of print.ABSTRACTDye contamination in printing and dyeing wastewater has long been a major concern due to its serious impact on both the environment and human health. In the quest for bioremediation of these hazardous dyes, biological resources such as biodegradation bacteria and enzymes have been investigated in severely polluted environments. In this context, the triphenylmethane transporter gene (tmt) was identified in six distinct clones from a metagenomic library of the printing and dyeing wastewater treatment system. Escherichia coli expressi...
Source: Biotechnology Letters - April 25, 2024 Category: Biotechnology Authors: Zhou Wang Haoqiang Zhou Yilan Cheng Lijin An Dazhong Yan Hongjun Chao Jing Wu Source Type: research
Availability of drugs for the treatment of multidrug-resistant/rifampicin-resistant tuberculosis in the World Health Organization European Region, October 2023
The BPaLM regimen (bedaquiline, pretomanid, linezolid and moxifloxacin) recently recommended by the World Health Organization offers short, safe, and effective treatment for multidrug-resistant/rifampicin-resistant tuberculosis (TB). In a survey with national TB focal points in 18 central and western European countries to explore barriers for the implementation of BPaLM, only three reported full availability of pretomanid, a necessary component of this regimen. Implementation barriers included financing and procurement. Solutions on national and supranational level are needed to guarantee universal access. (Source: Eurosurveillance)
Source: Eurosurveillance - April 25, 2024 Category: Infectious Diseases Authors: Ralf Otto-Knapp, Suzanne Edwards, Giorgi Kuchukhidze, Stefan Kr öger, Brit Häcker, Stela Bivol and Askar Yedilbayev Source Type: research
High prevalence of plasmid-mediated quinolone resistance in escherichia coli strains producing extended-spectrum beta-lactamases isolated from faeces and urine of pregnant women with acute cystitis
CONCLUSION: This study revealed a high rate of resistance to the quinolone nalidixic acid and a widespread distribution of PMQR genes in MDR E. coli strains producing ESBLs. The strains represented virulence factors and phylogenetic group B2 are closely associated with abundance in UTI and faeces. However, the predominant clones in faeces were not found in UTIs and it is possible that rep-PCR is not sufficiently discriminating clones.PMID:38656625 | DOI:10.1007/s11033-024-09491-9 (Source: Molecular Biology Reports)
Source: Molecular Biology Reports - April 24, 2024 Category: Molecular Biology Authors: Maryam Sohrabi Javad Fathi Samane Mohebi Zahra Hashemizadeh Soudeh Kholdi Mahtab Hadadi Kowsar Keshavarz Zahra Darvishvand Source Type: research
Genetic diversity of KPC-2-producing Klebsiella pneumoniae complex from aquatic ecosystems
In this study,blaKPC-2-positiveKlebsiella pneumoniae complex strains were isolated from different anthropogenically affected aquatic ecosystems and characterized using phenotypic, molecular, and genomic methods.K. pneumoniae complex strains exhibited multidrug-resistant and extensively drug-resistant profiles, spotlighting the resistance to carbapenems, ceftazidime-avibactam, colistin, and tigecycline, which are recognized as last-line antimicrobial treatment options. Molecular analysis showed the presence of several antimicrobial resistance, virulence, and metal tolerance genes. In-depth analysis showed that theblaKPC-2 g...
Source: World Journal of Microbiology and Biotechnology - April 24, 2024 Category: Microbiology Source Type: research
High prevalence of multidrug-resistant Enterobacterales carrying extended-spectrum beta-lactamase and AmpC genes isolated from neonatal sepsis in Ahvaz, Iran
This study aimed ... (Source: BMC Microbiology)
Source: BMC Microbiology - April 24, 2024 Category: Microbiology Authors: Sima Mansouri, Mohammad Savari, Arash Malakian and Effat Abbasi Montazeri Tags: Research Source Type: research
Recurrent Chagas' disease meningomyelitis in an HIV-infected patient
We report a 59-year-old man native from the Northeast region of Brazil, with a second episode of subacute chagasic meningomyelitis. He had long-term multidrug-resistant HIV and had abandoned combined antiretroviral therapy (CD4+ lymphocyte count, 16 cells/mm³, and HIV viral load 169 403 copies/mL). He initially received benznidazole but switched to nifurtimox after developing myelotoxicity. He was discharged home having made a partial neurological improvement. Chagas' disease should be included in the differential diagnosis of meningomyelitis in people living with HIV/AIDS who are from endemic areas of this parasitic dise...
Source: Practical Neurology - April 23, 2024 Category: Neurology Authors: Igor Melo de Almeida Aline Borges Moreira da Rocha Jos é Angelo Lauletta Lindoso Vera L úcia Teixeira de Freitas Augusto Cp Oliveira Jose E Vidal Source Type: research
Comparative analysis of the antimicrobial resistance and virulence traits in ESBL-producing-Klebsiella pneumoniae ST307 strains colonizing the gastrointestinal tract and causing a fatal bloodstream infection in a leukemia patient
Infect Genet Evol. 2024 Apr 21:105598. doi: 10.1016/j.meegid.2024.105598. Online ahead of print.ABSTRACTKlebsiella pneumoniae is an opportunistic pathogen that can colonize the gastrointestinal tract (GIT) of humans. The mechanisms underlying the successful translocation of this pathogen to cause extra-intestinal infections remain unknown, although virulence and antimicrobial resistance traits likely play significant roles in the establishment of infections. We investigated K. pneumoniae strains isolated from GIT colonization (strains Kp_FZcol-1, Kp_FZcol-2 and Kp_FZcro-1) and from a fatal bloodstream infection (strain Kp_...
Source: Infection, Genetics and Evolution - April 23, 2024 Category: Genetics & Stem Cells Authors: Luana Boff Humberl ânia de Sousa Duarte Gabriela Bergiante Kraychete Gabriel Taddeucci-Rocha Bianca Diniz Oliveira Rodolpho Mattos Albano Ana Paula D'Alincourt Carvalho-Assef Silvana Vargas Superti Ianick Souto Martins Renata Cristina Pic ão Source Type: research
Application of Mono and Trinuclear Cyclometalated Iridium (III) Complexes in Differential Bacterial Imaging and Antimicrobial Photodynamic therapy
Chemistry. 2024 Apr 23:e202400646. doi: 10.1002/chem.202400646. Online ahead of print.ABSTRACTThe application of transition metal complexes for antimicrobial photodynamic therapy (PDT) has emerged as an attractive alternative in mitigating a broad range of bacterial pathogens, including multidrug-resistant pathogens. In view of their photostability, long excited-state lifetimes, and tunable emission properties, transition metal complexes also contribute as bioimaging agents. In the present work, we designed mono and trinuclear cyclometalated iridium(III) complexes to explore their imaging application and antibacterial pote...
Source: Chemistry - April 23, 2024 Category: Chemistry Authors: Bishnu Das Prakash Biswas Amirul Islam Mallick Parna Gupta Source Type: research
Development of an efficient liposomal DOX delivery formulation for HCC therapy by targeting CK2 α
Biotechnol J. 2024 Apr;19(4):e2400050. doi: 10.1002/biot.202400050.ABSTRACTHepatocellular carcinoma (HCC) is a digestive tract cancer with high mortality and poor prognosis, especially in China. Current chemotherapeutic drugs lead to poor prognosis, low efficacy, and high side effects due to weak targeting specificity and rapidly formed multidrug resistance (MDR). Based on the previous studies on the doxorubicin (DOX) formulation for cancer targeting therapy, we developed a novel DOX delivery formulation for the targeting chemotherapy of HCC and DOX resistant HCC. HCSP4 was previously screened and casein kinase 2α (CK2α)...
Source: Biotechnology Journal - April 23, 2024 Category: Biotechnology Authors: Ruixia Zhao Sinan Cheng Xue Bai Danying Zhang Hongming Fang Wanlin Che Wenxuan Zhang Yujuan Zhou Wei Duan Qiumin Liang Li Xiao Guochao Nie Yingchun Hou Source Type: research
Recurrent Chagas' disease meningomyelitis in an HIV-infected patient
We report a 59-year-old man native from the Northeast region of Brazil, with a second episode of subacute chagasic meningomyelitis. He had long-term multidrug-resistant HIV and had abandoned combined antiretroviral therapy (CD4+ lymphocyte count, 16 cells/mm³, and HIV viral load 169 403 copies/mL). He initially received benznidazole but switched to nifurtimox after developing myelotoxicity. He was discharged home having made a partial neurological improvement. Chagas' disease should be included in the differential diagnosis of meningomyelitis in people living with HIV/AIDS who are from endemic areas of this parasitic dise...
Source: Practical Neurology - April 23, 2024 Category: Neurology Authors: Igor Melo de Almeida Aline Borges Moreira da Rocha Jos é Angelo Lauletta Lindoso Vera L úcia Teixeira de Freitas Augusto Cp Oliveira Jose E Vidal Source Type: research
Comparative analysis of the antimicrobial resistance and virulence traits in ESBL-producing-Klebsiella pneumoniae ST307 strains colonizing the gastrointestinal tract and causing a fatal bloodstream infection in a leukemia patient
Infect Genet Evol. 2024 Apr 21:105598. doi: 10.1016/j.meegid.2024.105598. Online ahead of print.ABSTRACTKlebsiella pneumoniae is an opportunistic pathogen that can colonize the gastrointestinal tract (GIT) of humans. The mechanisms underlying the successful translocation of this pathogen to cause extra-intestinal infections remain unknown, although virulence and antimicrobial resistance traits likely play significant roles in the establishment of infections. We investigated K. pneumoniae strains isolated from GIT colonization (strains Kp_FZcol-1, Kp_FZcol-2 and Kp_FZcro-1) and from a fatal bloodstream infection (strain Kp_...
Source: Infection, Genetics and Evolution - April 23, 2024 Category: Genetics & Stem Cells Authors: Luana Boff Humberl ânia de Sousa Duarte Gabriela Bergiante Kraychete Gabriel Taddeucci-Rocha Bianca Diniz Oliveira Rodolpho Mattos Albano Ana Paula D'Alincourt Carvalho-Assef Silvana Vargas Superti Ianick Souto Martins Renata Cristina Pic ão Source Type: research
