Deguelin exhibits potent apoptotic and antiangiogenic activities in a variety of transformed cells and cancer cells. Deguelin also exhibits potent tumor suppressive effects in xenograft tumor models for many human cancers. Our initial studies confirmed that deguelin disrupts ATP binding to HSP90 and consequently induces destabilization of its client proteins such as HIF-1α. Interestingly, a fluorescence probe assay revealed that deguelin and its analogues do not compete with ATP binding to the N-terminus of HSP90, unlike most HSP90 inhibitors. To determine the key parts of deguelin that contribute to its potent HSP90 inhibition, as well as its antiproliferative and antiangiogenic activities, we have established a structure-activity relationship (SAR) of deguelin. In the course of these studies, we identified a series of novel and potent HSP90 inhibitors. In particular, analogues 54 and 69, the B- and C-ring-truncated compounds, exhibited excellent antiproliferative activities with IC(50) of 140 and 490 nM in the H1299 cell line, respectively, and antiangiogenic activities in zebrafish embryos in a dose dependent manner (0.25-1.25 μM).

The Hsp90 facilitates proper folding of signaling proteins associated with cancer progression, gaining attention as a target for therapeutic intervention.

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The first total syntheses of the bioactive cyclodepsipeptides ohmyungsamycin A and B are described. Key features of our synthesis include the concise preparation of a linear cyclization precursor that consists of N-methyl amides and non-proteinogenic amino acids, and its macrolactamization from a bent conformation. The proposed structure of ohmyungsamycin B was revised based on its synthesis. The cyclic core of the ohmyungsamycins was shown to be responsible for the excellent antituberculosis activity, and ohmyungsamycin variants with truncated chains were evaluated for their biological activity.

Ocular diseases featuring pathologic neovascularization are the leading cause of blindness, and anti-VEGF agents have been conventionally used to treat these diseases. Recently, regulating factors upstream of VEGF, such as HIF-1α, have emerged as a desirable therapeutic approach because the use of anti-VEGF agents is currently being reconsidered due to the VEGF action as a trophic factor. Here, we report a novel scaffold discovered through the complete structure−activity relationship of ring-truncated deguelin analogs in HIF-1α inhibition. Interestingly, analog 6i possessing a 2-fluorobenzene moiety instead of a dimethoxybenzene moiety exhibited excellent HIF-1α inhibitory activity, with an IC 50 value of 100 nM. In particular, the further ring-truncated analog 34f, which showed enhanced HIF-1α inhibitory activity compared to analog 2 previously reported by us, inhibited in vitro angiogenesis and effectively suppressed hypoxia-mediated retinal neovascularization. Importantly, the heteroatom-substituted benzene ring as a key structural feature of analog 34f was identified as a novel scaffold for HIF-1α inhibitors that can be used in lieu of a chromene ring.

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This paper presents a high-speed Forward Error Correction (FEC) architecture based on two-parallel Reed-Solomon (RS) decoder for 10 and 40-Gb/s optical communication systems. A highspeed two-parallel RS(255, 239) decoder has been proposed and the derived structure can also be applied to implement the 10 and 40-Gb/s RS FEC architectures. The implementation results show that 16-Ch. RS FEC architecture can operate at a clock frequency of 160 MHz and has a throughput of 41 Gb/s for the Xilinx Virtex4 FPGA. Also, RS FEC operates at a clock frequency of 400 MHz and has a throughput of 102 Gb/s for 0.18-μm CMOS technology.