bortezomib and Neoplasms

Marine natural products are known for their diverse chemical structures and extensive bioactivities. Renieramycins, the member of tetrahydroisoquinoline family of marine natural products, arouse interests because of their strong antitumor activities and similar structures to the first marine antitumor agent ecteinascidin-743, approved by the European Union. According to the literatures, researches on the pharmacological activities of renieramycins mainly focus on their antitumor activities. In addition, by structural modification, derivatives of renieramycins show stronger antiproliferative activity and less accidental necrosis activity on cells. Nevertheless, the difficulties in extraction and separation hinder their further development. Hence, the synthetic chemistry work of renieramycins plays a key role in their further development. In this review, currently reported researches on the synthetic chemistry, pharmacological activities and structural modification of renieramycins are summarized, which will benefit future drug development and innovation.

Topics: Alkaloids; Anti-Infective Agents; Antibiotics, Antineoplastic; Antiprotozoal Agents; Biological Products; Molecular Structure; Neoplasms; Tetrahydroisoquinolines

A series of novel non-covalent peptidomimetic proteasome inhibitors possessing bulky group at the C-terminus and N-alkylation at the N-terminus were designed with the aim to increase metabolic stabilities in vivo. All the target compounds were screened for their inhibitory activities against human 20S proteasome, and most analogs exhibited notable potency compared with the positive control bortezomib with IC

Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Humans; Neoplasms; Peptidomimetics; Proteasome Endopeptidase Complex; Proteasome Inhibitors; Reproducibility of Results

The proteasome plays a crucial role in degradation of normal proteins that happen to be constitutively or inducibly unstable, and in this capacity it plays a regulatory role. Additionally, it degrades abnormal/damaged/mutant/misfolded proteins, which serves a quality-control function. Inhibitors of the proteasome have been validated in the treatment of multiple myeloma, with several FDA-approved therapeutics. Rpn11 is a Zn

Topics: Cell Line; Cell Line, Tumor; Cell Proliferation; Drug Discovery; Humans; Models, Molecular; Neoplasms; Proteasome Endopeptidase Complex; Proteasome Inhibitors; Quinolines; Trans-Activators; Zinc

The activation of the NF-κB transcription factor is a major adaptive response induced upon treatment with EGFR kinase inhibitors, leading to the emergence of resistance in nonsmall cell lung cancer and other tumor types. To suppress this survival mechanism, we developed new thiourea quinazoline derivatives that are dual inhibitors of both EGFR kinase and the NF-κB activity. Optimization of the hit compound, identified in a NF-κB reporter gene assay, led to compound 9b, exhibiting a cellular IC

Topics: Animals; Antineoplastic Agents; Breast; Breast Neoplasms; Cell Line, Tumor; ErbB Receptors; Female; Human Umbilical Vein Endothelial Cells; Humans; Mice; Mice, Nude; Neoplasms; NF-kappa B; Quinazolines; Signal Transduction; Thiourea

A series of azobenzene-containing peptidic boronate esters was prepared and the activity of the thermally adapted states (TAS), enriched in trans isomer, and the photostationary states (PSS), enriched in cis isomer, for each compound were evaluated against β5 and β1 proteasome subunits. Compounds with a sterically demanding phenyl-substituted azobenzene at P2 (4c), and a less sterically demanding unsubstituted azobenzene at the N-terminus (5a), showed the greatest difference in activity between the two states. In both cases, the more active trans-enriched TAS had activity comparable to bortezomib and delanzomib. Furthermore, cis-enriched 4c inhibited tumor growth in both breast and colorectal carcinoma cell lines. Significantly, the initial trans-enriched TAS of 4c was not cytotoxic against the non-malignant MCF-10A cells.

Topics: Antineoplastic Agents; Azo Compounds; Cell Line, Tumor; Cell Proliferation; Humans; Isomerism; Neoplasms; Photochemical Processes; Proteasome Endopeptidase Complex; Proteasome Inhibitors