SC-560 and mofezolac isosteres as new potent COX-1 selective inhibitors with antiplatelet effect.

Selective cyclooxygenase (COX)-1 inhibitors can be employed as potential cardioprotective drugs. Moreover, COX-1 plays a key role in inflammatory processes and its activity is associated with some types of cancer. In this work, we designed and synthesized a set of compounds that structurally mimic the selective COX-1 inhibitors, SC-560 and mofezolac, the central cores of which were replaced either with triazole or benzene rings.

An Endoplasmic Reticulum Specific Pro-amplifier of Reactive Oxygen Species in Cancer Cells.

The folding and export of proteins and hydrolysis of unfolded proteins are disbalanced in the endoplasmic reticulum (ER) of cancer cells, leading to so-called ER stress. Agents further augmenting this effect are used as anticancer drugs including clinically approved proteasome inhibitors bortezomib and carfilzomib. However, these drugs can affect normal cells, which also rely strongly on ER functions, leading, for example, to accumulation of reactive oxygen species (ROS).

Synthesis, inhibitory activity and in silico docking of dual COX/5-LOX inhibitors with quinone and resorcinol core.

Based on the significant anti-inflammatory activity of natural quinone primin (5a), series of 1,4-benzoquinones, hydroquinones, and related resorcinols were designed, synthesized, characterized and tested for their ability to inhibit the activity of cyclooxygenase (COX-1 and COX-2) and 5-lipoxygenase (5-LOX) enzymes. Structural modifications resulted in the identification of two compounds 5b (2-methoxy-6-undecyl-1,4-benzoquinone) and 6b (2-methoxy-6-undecyl-1,4-hydroquinone) as potent dual COX/5-LOX inhibitors. The IC values evaluated in vitro using enzymatic assay were for compound 5b IC = 1.

Lysosome-Targeting Amplifiers of Reactive Oxygen Species as Anticancer Prodrugs.

Cancer cells produce elevated levels of reactive oxygen species, which has been used to design cancer specific prodrugs. Their activation relies on at least a bimolecular process, in which a prodrug reacts with ROS. However, at low micromolar concentrations of the prodrugs and ROS, the activation is usually inefficient.

Synthesis of Tetracyclic Diterpenoids with Pharmacologic Relevance.

This review covers the chemical reactions, synthesis, and biological activities of tetracyclic diterpenoids including ent-kauranes, ent-beyeranes, ent-atisanes, ingenanes, tyglianes, stemodanes, stemaranes, sordarin, salvileucalin B, harringtonolide and hainanolidol. It comprises of the un-reviewed references from the year 2000.

Fluorescent castasterone reveals BRI1 signaling from the plasma membrane.

Receptor-mediated endocytosis is an integral part of signal transduction as it mediates signal attenuation and provides spatial and temporal dimensions to signaling events. One of the best-studied leucine-rich repeat receptor-like kinases in plants, BRASSINOSTEROID INSENSITIVE 1 (BRI1), perceives its ligand, the brassinosteroid (BR) hormone, at the cell surface and is constitutively endocytosed. However, the importance of endocytosis for BR signaling remains unclear.

Photochemistry of flavonoids.

Flavonoids and their photochemical transformations play an important role in biological processes in nature. Synthetic photochemistry allows access to molecules that cannot be obtained via more conventional methods. This review covers all published synthetic photochemical transformations of the different classes of flavonoids.

Total synthesis and antiproliferative activity screening of (+/-)-aplicyanins A, B and E and related analogues.

The first total synthesis of the indole alkaloids (+/-)-aplicyanins A, B, and E, plus 17 analogues, all in racemic form, is reported. Modifications to the parent compound included changing the number of bromine substituents on the indole, the nature of the substituents on the indole nitrogen (H, Me, or OMe), and/or the oxidation level of the heterocyclic core tetrahydropyrimidine. Each compound was screened against three human tumor cell lines, and 14 of the newly synthesized compounds showed considerable cytotoxicity.

Brassinolide activities of 2alpha,3alpha-diols versus 3alpha,4alpha-diols in the bean second internode bioassay: explanation by molecular modeling methods.

In general, the structural requirements postulated for a high brassinolide activity are: 2alpha,3alpha-diol, 6-ketone or better 7-oxalactone in B-ring, A/B trans fused ring junction, a cis C-22,C-23-diol preferentially with RR configurations, and a C-24 methyl or ethyl substituent [Takatsuto S, Yazawa N, Ikekawa N, Takematsu T, Takeuchi Y, Koguchi M. Structure-activity relationship of brassinosteroids. Phytochemistry 1983;22:2437-41; Thompson MJ, Meudt WJ, Mandava NB, Dutky SR, Lusby WR, Spaulding DW.

Syntheses of new androstane brassinosteroids with 17beta-ester groups--butyrates, heptafluorobutyrates, and laurates.

New androstane brassinosteroids with 17beta-ester groups - butyrates, heptafluorobutyrates, and laurates (4-18) - were prepared. Brassinolide activity was evaluated using both the bean second internode bioassay and the rice lamina inclination test. Brassinosteroid 16 was found to be the most active by the bean second internode bioassay.