The high potency of the tetrahydrofuran-containing acetogenins (THF-ACGs) against a broad range of human cancer cell lines has stimulated interest in structurally simpler mimetics. In this context, we have previously reported THF-ACG mimetics in which the THF and butenolide moieties of a mono-THF-ACG were replaced with carbohydrate and thiophene residues, respectively. In the present study, towards the targeting of these carbohydrate analogues to prostate cancer (PCa), we synthesized prodrugs in which a parent thiophene or butenolide congener was conjugated through a self-immolative linker to 2-[3-(1,3-dicarboxypropyl)ureido] pentanedioic acid (DUPA), a highly specific ligand for prostate-specific membrane antigen (PSMA), which is overexpressed on prostate tumors. Both prodrugs were found to be more active against receptor positive LNCaP than receptor-negative PC-3 cells, with 2.5 and 12 times greater selectivity for the more potent thiophene analog and the less active butenolide congener, respectively. This selectivity for LNCaP over PC-3 contrasted with the behavior of the parent drugs, which showed similar or significantly higher activity for PC-3 compared to LNCaP. These data support the notion that higher activity of these DUPA-derived prodrugs against LNCaP cells is connected to their binding to PSMA and suggest that the conjugation of PSMA ligands to this family of cytotoxic agents may be effective for targeting them to PCa.
This paper presents a primary droop current-sharing controller that can integrate into voltage feedback controller and, thus, provides a low-cost and simple solution for parallel DC/DC converters system. From the equivalent small-signal model, a twoport network was adapted to describe the output and control variables for designing voltage and droop current-sharing loops. From the analysis results, the designed primary droop current-sharing controller will not affect the original voltage loop gain profile to let the DC/DC converter preserve desire control performance. After designing a stable DC/DC converter with primary droop current-sharing control, the stability of the interconnected parallel DC/DC converters system was studied. When the cable resistance is reduced, when the cable resistance is reduced, the interconnected system might be unstable. Finally, some simulation and experimental results demonstrated the effectiveness of the proposed controller in a prototype parallel DC/DC converters system.
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