Guanidinobenzoatase (GB) is a cell surface proteolytic enzyme capable of degrading fibronectin, and is associated with tumour cells and cells capable of migration. The location of active GB in sections has been demonstrated with 9-aminoacridine (9-AA), a competitive inhibitor of GB. 3,4-Dichloroisocoumarin (3,4-DCI) and pentamidine isethionate (PI) are inhibitors of trypsin-like enzymes. It has now been demonstrated that 3,4-DCI, PI, and guanidino derivative compounds are significant inhibitors of GB, on the surfaces of lung squamous cell carcinoma cells in frozen sections and free GB in solution. Dexamethasone acetate (DMA) and medroxy-progesterone (MP) did not show any significant inhibition of GB activity. These molecules lack a reactive chloride or guanidino groups and are thought to react at the nuclear level, rather than directly on this cell surface protease. Kinetic studies have shown that 3,4-DCI, PI and guanidino derivatives are reversible competitive inhibitors of GB, as determined in vitro on the purified enzyme. The inhibition resulting with 3,4-DCI was a time-dependent process. It is suggested that these inhibitors interact with GB by binding to its active site, resulting in the formation of enzyme-inhibiter complexes (GB-I). The GB-I complexes can be dissociated with SDS treatment, resulting in the regain of GB activity.
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http://dx.doi.org/10.3109/14756369409020203 | DOI Listing |
Commun Biol
December 2024
Manufacturing, CSIRO, 343 Royal Parade, Parkville, VIC, 3052, Australia.
The antibiotic 2-nitroimidazole (2NI) or azomycin, used for treating drug-resistant tuberculosis and imaging tumor hypoxia, requires activation by bacterial nitroreductases for its antibiotic and cytotoxic effect. Mycobacterium sp. JS330 produces 2-nitroimidazole nitrohydrolase (NnhA) that circumvents 2NI activation, conferring 2NI resistance by hydrolysing it to nitrite and imidazol-2-one (IM2O) instead.
View Article and Find Full Text PDFBiochim Biophys Acta Gen Subj
February 2025
Department of Chemistry, York College of the City University of New York, Jamaica, New York 11451, USA; PhD Programs in Chemistry and Biochemistry, Graduate Center of the City University of New York, New York 10016, USA. Electronic address:
Atherosclerosis, the major underlying cause of cardiovascular disease, is believed to arise from the accumulation of low-density lipoprotein (LDL) in the arterial subendothelial space, ultimately leading to plaque formation. It is proposed that the accumulation of LDL is linked to its intrinsic aggregation propensity. Although the native LDL is not prone to aggregation, LDL(-), an electronegative LDL characterized in the plasma, has been shown to prime LDL aggregation in a domino-like behavior similar to amyloidogenic proteins.
View Article and Find Full Text PDFOrg Biomol Chem
November 2024
Universitat Rovira i Virgili, Departament de Química Analítica i Química Orgànica, Faculty of Chemistry, C/Marcel·lí Domingo 1, 43007 Tarragona, Spain.
This study focuses on the stereoselective syntheses of 1-deoxysphingosine analogues as potential inhibitors of sphingosine kinase (SphK), particularly targeting its isoforms SphK1 and SphK2, which are implicated in cancer progression and therapy resistance. The research builds on previous work by designing a series of analogues featuring systematic structural modifications like the incorporation of a triazole ring, varying degrees of fluorination, and different head groups (, guanidino, -methylamino, and ,-dimethylamino). These modifications aimed to enhance polar and hydrophobic interactions especially with SphK2.
View Article and Find Full Text PDFBioorg Med Chem
December 2024
Lab of Chemical Biology and Molecular Drug Design, College of Pharmaceutical Science, Zhejiang University of Technology, Deqing 313299, China; Institute of Drug Development & Chemical Biology, Zhejiang University of Technology, Deqing 313299, China; Zhejiang Jieyuan Med-Tech Co., Ltd., Hangzhou, 311113, China. Electronic address:
Transmembrane Serine Protease 2 (TMPRSS2) plays a critical role in tumorigenesis and progression, making its degradation a promising therapeutic strategy. In this study, we designed and synthesized TMPRSS2-PROTACs, including VPOT64 and VPOT76, based on camostat. Both compounds exhibited superior inhibitory effects on HT-29 colorectal and Calu-3 lung cancer cells compared to paclitaxel.
View Article and Find Full Text PDFEnviron Res
December 2024
Department of Pharmacy, Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang 324000, PR China. Electronic address:
Recent studies have demonstrated the widespread presence of 1,3-diphenylguanidine (DPG) and its derivatives in environmental matrices. While, the amount of human exposure to these rubber additives remains unclear. In this study, we collected human urine samples from healthy general adults (n = 221) living in Quzhou, China, and analyzed these samples for DPG and its five derivatives.
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