Synthesis and Evaluation of Dibenzothiophene Analogues as Pin1 Inhibitors for Cervical Cancer Therapy.

The peptidyl-prolyl isomerase Pin1 is correlated with the progression of cervical cancer via regulating numerous oncogenic and tumor suppressor pathways. p65 is a crucial regulator of tumorigenesis that is regulated by Pin1, and p65 signaling suppression can enhance the antitumor efficacy of doxorubicin (DOX). Here, we utilized a structural mimicry approach to synthesize a series of dibenzothiophene analogues and evaluated their ability to inhibit Pin1 activity. Compound 1a was identified as a potent Pin1 inhibitor that inhibited p65 signaling in vitro and in cervical cancer cells. Moreover, compound 1a enhanced the cytotoxicity of DOX in cervical cancer cells via reducing p65 nuclear accumulation and enhancing DOX uptake. These compounds are promising scaffolds for developing more potent Pin1 inhibitors against cervical cancer, either alone or in combination with anticancer drugs such as DOX.

An iridium(III) complex/G-quadruplex ensemble for detection of ochratoxin A based on long-lifetime luminescent.

A G-quadruplex-based platform has been developed for the time-resolved monitoring of ochratoxin A (OTA). The simple platform displays good sensitivity for OTA with a detection limit of 40 nM via steady-state emission spectroscopy. Notably, the platform showed a detection limit of 10.8 nM via time-resolved emission spectroscopy (TRES), which is about 4 times more sensitive than steady-state mode. Moreover, the probe showed excellent selectivity for OTA over other mycotoxins. Furthermore, OTA was successfully detected in actual herbal plant extracts samples. Our platform is the first to detect OTA using TRES to distinguish between the target signals versus the auto-fluorescence of real samples. This platform shows improved detection speed, accuracy and sensitivity with simple operation, low cost, and no requirement for complicated pre-processing.

Iridium(III)-based chemosensors for the detection of metal ions.

In recent years, transition metal complexes with their prominent photophysical properties have emerged as versatile chemosensors to probe different target analytes, including metal ions. By incorporating specific metal ion receptors, various iridium(III) complex-based cation sensors have been developed using different mechanisms. In this review, we survey examples of iridium(III) complex-based metal ion chemosensors that have been reported in the literature. Their design, mechanism and outlook will also be discussed.

Pharmacological Inhibition of LSD1 for Cancer Treatment.

Lysine-specific demethylase 1A (LSD1, also named KDM1A) is a demethylase that can remove methyl groups from histones H3K4me1/2 and H3K9me1/2. It is aberrantly expressed in many cancers, where it impedes differentiation and contributes to cancer cell proliferation, cell metastasis and invasiveness, and is associated with inferior prognosis. Pharmacological inhibition of LSD1 has been reported to significantly attenuate tumor progression in vitro and in vivo in a range of solid tumors and acute myeloid leukemia. This review will present the structural aspects of LSD1, its role in carcinogenesis, a comparison of currently available approaches for screening LSD1 inhibitors, a classification of LSD1 inhibitors, and its potential as a drug target in cancer therapy.

Iridium(iii) complexes as reaction based chemosensors for medical diagnostics.

Transition metal complexes have attracted interest in the fields of cancer therapy, medical and environmental detection, and materials of organic light-emitting diodes (OLED). Recently, iridium(iii) complexes have been explored in a reaction based way for luminescence monitoring and imaging due to their salient photophysical properties, including large Stokes shifts, long-lived luminescence and high luminescent quantum yields. This frontier article will introduce recent developments and applications of iridium(iii) complexes as luminescent probes for ions and biomolecules. Our outlook for this class of complexes is also discussed.

Identification of a rhodium(iii) complex as a Wee1 inhibitor against TP53-mutated triple-negative breast cancer cells.

The rhodium(iii) complex 1 was identified as a potent Wee1 inhibitor in vitro and in cellulo. It decreased Wee1 activity and unscheduled mitotic entry, and induced cell damage and death in TP53-mutated triple-negative breast cancer cells. 1 represents a promising scaffold for further development of more potent metal-based Wee1 antagonists.

A long-lifetime iridium(iii) complex for lysosome tracking with high specificity and a large Stokes shift.

Investigating the role of lysosome dysfunction in cancer requires the development of efficient probes for lysosomes. We report herein a cyclometalated iridium(iii) complex (Ir-Ly) as a luminescent probe for visualizing lysosomes in cancer cells. The morpholine and hydroxy moieties within Ir-Ly provide suitable hydrophilicity and responsiveness to pH. Importantly, Ir-Ly exhibits a large Stokes shift, long lifetime and high photostability, which are important advantages for lysosome tracking in living cells.

Physiologically stable vanadium(IV) porphyrins as a new class of anti-HIV agents.

The water soluble oxovanadium(IV) tetraarylporphyrin has demonstrated excellent solution stability against glutathione reduction and high potency (5 microM, 97% inhibition) in inhibiting HIV-1 replication in Hut/CCR5 cells.