Current Medicinal Chemistry - Volume 29, Issue 22, 2022

Although non-coding RNAs (ncRNAs) were initially thought to be a class of RNA transcripts with no encoding capability, it has been established that some ncRNAs actually contain open reading frames (ORFs), which can be translated into micropeptides or microproteins. Recent studies have reported that ncRNAs-derived micropeptides/ microproteins have regulatory functions on various biological and oncological processes. Some of these micropeptides/microproteins act as tumor inhibitors and some as tumor inducers. Understanding the carcinogenic role of ncRNAs-encoded micropeptides/ microproteins seems to pose potential challenges to cancer research and offer promising practical perspectives on cancer treatment. In this review, we summarized the present information on the association of ncRNAs-derived micropeptides/microproteins with different types of human cancers. We also mentioned their carcinogenic mechanisms in cancer metabolism, signaling pathways, cell proliferation, angiogenesis, metastasis, and so on. Finally, we discussed the potential clinical value of these micropeptides/ microproteins and their potential use in the diagnosis and treatment of cancer. This information may help discover, optimize, and develop new tools based on biological micropeptides/ microproteins for the early diagnosis and development of anticancer drugs.

Vitamin D as a prohormone is converted into the active form in vivo and binds to vitamin D receptors, exercising a wide range of biological functions. Recent studies strongly support that vitamin D supplementation is associated with reduced cancer risk and a good prognosis. Gastrointestinal cancer is the leading cause of cancer-related deaths worldwide. The key role of vitamin D in the development of gastrointestinal cancer has been observed. Moreover, Vitamin D can also affect innate immunity and perform anti-inflammation and anti-infection actions. Given the intimate relationship between cancer and inflammation, we herein summarize epidemiological and preclinical studies of vitamin D and the underlying mechanism of its action in inflammation, gastric and colorectal cancer by our group and other researchers. A beneficial effect of vitamin D in cancer and inflammatory disease has been supported by different studies. More controlled and larger clinical trials are needed before a reliable conclusion and realization of vitamin D supplementation in the adjunct treatment of gastrointestinal inflammation and cancer.

The present review focuses on the synthesis of cyclic 5′-deoxynucleoside phosphonate analogs. The formation of various phosphonate alkyl moieties is accomplished through (i) Wittig (or HWE) type condensation to the nucleoside aldehyde moiety; (ii) nucleophilic displacement reaction using phosphonate anion or Lewis acid; (iii) Arbuzov reaction; (iv) olefin cross-metathesis between vinyl phosphonates and vinylated nucleosides; and (v) radical reaction and Pd catalyzed alkyne. For the coupling of nucleobases with cyclic moieties, the Mitsunobu reaction and Sonogashira-type cross-coupling are usually applied. For the coupling of furanose moieties with nucleobases, Vorbrüggentype condensation is generally applied. Addition reactions mediated by selenium ions are mainly applied for the coupling of carbocyclic moieties. Their biological activity results have been summarized.

Estrogen receptors (ERs) are steroid hormone receptors, which belong to a large nuclear receptor family. Endocrine diseases correlate strongly with dysregulated ER signaling. Traditional therapies continue to rely on small molecule inhibitors, including aromatase inhibitors (AIs) and selective estrogen receptor modulators (SERMs), all of which permit acquired resistance to endocrine therapy. Proteolytic targeting chimeras (PROTACs) offer unprecedented potential for solving acquired endocrine resistance. ARV-471, an ER-targeting PROTAC developed by Arvinas, was designated as an Investigational New Drug by the US FDA in 2019, and a phase I trial in patients suffering from locally advanced or metastatic ER-positive/HER2- negative breast cancer was initiated. In this review, we will focus on progress in developing ER-targeting PROTACs from publications and patents aimed at the treatment of endocrine diseases.

Background: Parkinson’s disease (PD) is a long-term, degenerative, and neurological disease in which a person loses control of certain body functions. The formulation of novel effective therapeutics for PD as a neurodegenerative disease requires accurate and efficient diagnosis at the early stages. Objective: Analyzing data gathered by measurable signals converted from biological reactions allows for qualitative and quantitative evaluations. Among various approaches reported so far, biosensors are powerful analytical tools that have been used in detecting the biomarkers of PD. Methods: Biosensor’s biological recognition components include antibodies, receptors, microorganisms, nucleic acids, enzymes, cells and tissues, and biomimetic structures. This review introduces electrochemical, optical, and optochemical detection of PD biomarkers based on recent advances in nanotechnology and material science, which resulted in the development of high-performance biosensors in this field. Results: PD biomarkers such as α-synuclein protein, dopamine (DA), urate, ascorbic acid, miRNAs, and their biological roles are summarized. Additionally, the advantages and disadvantages of the usual standard methods are reviewed. We compared electrochemical, optical, and optochemical biosensors' properties and novel strategies for higher sensitivity and selectivity. Conclusion: The development of novel biosensors is required for the early diagnosis of PD as sensitive, rapid, reliable, and cost-effective systems.

Background: The importance of the role of NF-ΚB is recognized in situations such as malignant transformation and metastasis of cancer, and it has been suggested that inhibiting this role can be one of the cancer treatment strategies. Gold preparations such as auranofin are known to have an indirect NF-ΚB inhibitory effect. Objective: We synthesized a novel gold complex [tiopronin monovalent gold-5-mercapto- 1-methyl tetrazole, abbreviated as TPN-Au(I)-MM4], with different physical properties and chemical structure from auranofin, and evaluated its cytotoxic activity and radiation sensitizing effect on human THP1 cells. Methods: The number of viable cells was counted by the trypan blue dye exclusion method. The cell death evaluation was performed by FITC-Annexin V+ and PI staining. In investigating the radiation sensitizing effect of TPN-Au(I)-MM4, this compound [10 or 25 μM] was added into the culture medium 1 h before X-ray irradiation. Results: In the cells treated with 25 μM TPN-Au(I)-MM4 for 72 h, a decrease in the proliferation of THP1 cells was observed [The relative values of viable cells in the control group and the 25 μM treatment group were approximately 6.8 and 4.2, respectively]. In the combination of 25 μM of the compound treatment and X-ray irradiation, an increase of approximately 3.0-fold was observed in 2 Gy irradiation and approximately 1.4-fold in 4 Gy irradiation as in comparison to the case of irradiation alone. Conclusion: These results suggest that TPN-Au(I)-MM4 reduces the proliferation of THP1 cells through the induction of cell death, and the combined use of TPN-Au(I)-MM4 and X-ray irradiation shows effective cytotoxicity against THP1 cells.