Identification of tanshinone I as a natural Cu(II) ionophore.

The development of Cu(II) ionophores for targeted disruption of aberrant redox homeostasis in cancer cells has been considered an appealing strategy in the field of anticancer research. This study presents the first identification of tanshinone I (Ts1), a natural o-quinone, as a Cu(II) ionophore. Structure-activity relationship studies on tanshinones and mechanistic investigations reveal that the presence of Cu(II) effectively promotes the tautomerization of Ts1 from its diketo to keto-enol forms, thereby facilitating its sequential proton-loss Cu(II) chelation, and enabling it to function as a Cu(II) ionophore due to its structural features including the presence of an o-quinone moiety, a benzyl hydrogen, and a large conjugated system.

A hydrogen peroxide-activated Cu(II) pro-ionophore strategy for modifying naphthazarin as a promising anticancer agent with high selectivity for generating ROS in HepG2 cells over in L02 cells.

Targeting redox vulnerability of cancer cells by pro-oxidants capable of generating reactive oxygen species (ROS) has surfaced as an important anticancer strategy. Due to the intrinsic narrow therapeutic window and other dangerous side effects of ROS generation, it is highly needed and challenging to develop pro-oxidative anticancer agents (PAAs) with high selectivity for generating ROS in cancer cells. Herein we report a hydrogen peroxide (HO)-activated Cu(II) pro-ionophore strategy to develop naphthazarin (Nap) as such type of PAAs based on the HO-mediated conversion of boronate to free phenol.

Mechanistic Study on Gold-Catalyzed Highly Selective Hydroamination of Alkylidenecyclopropanes.

Density functional theory calculations have been carried out to study the mechanism of the gold-catalyzed highly selective hydroamination of alkylidenecyclopropanes. Two main mechanisms (i.e.

Influence of side chain structure changes on antioxidant potency of the [6]-gingerol related compounds.

[6]-Gingerol and [6]-shogaol are the major pungent components in ginger with a variety of biological activities including antioxidant activity. To explore their structure determinants for antioxidant activity, we synthesized eight compounds differentiated by their side chains which are characteristic of the C1-C2 double bond, the C4-C5 double bond or the 5-OH, and the six- or twelve-carbon unbranched alkyl chain. Our results show that their antioxidant activity depends significantly on the side chain structure, the reaction mediums and substrates.

Tailoring 3,3'-dihydroxyisorenieratene to hydroxystilbene: finding a resveratrol analogue with increased antiproliferation activity and cell selectivity.

Four novel compounds were designed by "tailoring" 3,3'-dihydroxyisorenieratene (a natural carotenoid) based on an isoprene unit retention truncation strategy. Among them, the smallest molecule 1 (2,3,6,2',3',6'-hexamethyl-4,4'-dihydroxy-trans-stilbene) was concisely synthesized in a one-pot Stille-Heck tandem sequence, and surfaced as a promising lead molecule in terms of its selective antiproliferative activity mediated by blocking the NCI-H460 cell cycle in G1 phase. Additionally, theoretical calculations and cell uptake experiments indicate that the unique polymethylation pattern of compound 1 significantly induces a conformational change shift out of planarity and increases its cell uptake and metabolic stability.

[Suppression of murine EAE by triptolide is related to downregulation of INF-gamma and upregulation of IL-10 secretion in splenic lymphocytes].

Aim: To explore the therapeutic effectivity and the possible mechanism of triptolide (Tri) on experimental autoimmune encephalomyelitis (EAE).

Methods: All female C57BL/6 mice were randomly divided into EAE group (28), Tri treated group (20) and adjuvant group (18). Mice in EAE and treated groups were immunized with myelin oligodendrocyte glycoprotein peptides 35-55 (MOG(35-55);), adjuvant group was injected at the same time, but instead of MOG(35-55); with normal saline.

A novel mutation in the second half of the keratin 17 1A domain in a large pedigree with delayed-onset pachyonychia congenita type 2.

Pachyonychia congenita type 2 (PC-2), also known as Jackson-Lawler type PC, is an autosomal dominant disorder characterized by hypertrophic nail dystrophy associated with focal keratoderma and multiple pilosebaceous cysts. We report a large Chinese pedigree of typical delayed-onset PC-2 that includes 19 affected members. Direct sequencing of PCR products revealed a novel heterozygous 325A-->G mutation in the affected members.