Mini Reviews in Medicinal Chemistry - Volume 23, Issue 6, 2023

Background: Immune-related cutaneous diseases are a series of disorders, such as alopecia areata, psoriasis, atopic dermatitis, systemic lupus erythematosus and autoimmune bullous dermatoses. Vitamin D is a fat-soluble vitamin, which is known for its classical pleiotropic effect. Recent studies have found that vitamin D, after catalyzed into its biologically active form [1,25(OH) 2D], correlated with its receptor, vitamin D receptor, plays a vital role in multiple pathophysiological processes, including immune-related dermatoses. This review mainly summarizes evidence on the role of vitamin D/vitamin D receptor in immune-related cutaneous diseases and the potential therapeutic targets for skin disorders. Methods: We have carried out a comprehensive literature search in PubMed and Google Scholar databases using keywords like “vitamin D”, “vitamin D receptor”, “immune”, “psoriasis”, “atopic dermatitis”, “skin”, “systemic lupus erythematosus”, “alopecia areata” and “autoimmune bullous dermatoses”. Only articles related to the topic were included in this review. Conference, patent, graduation thesis and articles without available full text were excluded. Results: Vitamin D/vitamin D receptor is critical for skin in regulating the proliferation and differentiation of keratinocytes, keeping the integrity of the skin barrier as well as maintaining the homeostasis of the “skin's immune system”. Vitamin D deficiency/vitamin D receptor mutations are potential risk factors for some immune-related cutaneous diseases. Conclusion: Vitamin D is a pleiotropic hormone, which is important in the homeostasis of human body. Many studies have revealed vitamin D deficiency in several skin diseases. Thus, vitamin D supplementation may be a useful therapeutic option for immune-related skin diseases.

Background: Licorice is an important traditional Chinese medicine commonly used in clinical practice and contains more than 300 flavonoids. Chalcone is one of the main types of flavonoids with a wide range of biological functions and pharmacological activities. In the anticancer research, chalcone compounds have shown excellent performance. Objective: This review aims to summarize the biosynthetic pathway and pharmacokinetics of chalcone from licorice and provide evidence for the anticancer effects of chalcone and the underlying mechanisms involved. Methods: For this review, the following databases were consulted: the PubMed Database (https://pubmed.ncbi.nlm.nih.gov), Chinese National Knowledge Infrastructure (http:// www.cnki.net), National Science and Technology Library (http://www.nstl.gov.cn/), Wanfang Data (http://www.wanfangdata.com.cn/), and the Web of Science Database (http://apps.webofknowledge.com/). Results: To date, about 56 chalcones have been isolated and identified from licorice, 14 of which have antitumor effects. These chalcones have a wide range of biological activities and can inhibit the viability, proliferation, and migration of cancer cells by blocking the cancer cell cycle, thus inducing apoptosis and autophagy. However, the molecular mechanism of the anticancer effects of chalcone is not fully understood. Conclusion: In this paper, the molecular mechanism of chalcone regulating different types of cancer is reviewed in detail from the biosynthetic pathway. This comprehensive review article summarizes the biosynthetic pathway and pharmacokinetics of chalcone from the traditional Chinese medicine licorice and provides evidence for the potential anticancer effects of chalcone and the respective mechanisms of action. This paper also provides a basis for structural modification, biosynthesis, and new drug development of chalcone compounds in Glycyrrhiza uralensis.

Tuberculosis (TB) is an airborne infection caused by the bacteria Mycobacterium Tuberculosis (MTB). It mainly affects the lungs and causes severe coughing, fever, and chest pains. With the rising prevalence of drug-resistant and inactive Tuberculosis (TB), there is an essential need to discover more effective molecules capable of combating this heinous illness. Pyrazinamide is a first-line tuberculosis therapy that shortens prophylactic duration from twelve to six months. The majority of presently used tuberculosis medications were found by a mix of serendipity and innovative chemical alterations of an existing lead drug. Given that the majority of these discoveries occurred years ago, there is a definite need to use fresh methodologies and technology for discovery to meet the grave danger posed by tuberculosis and the rise of treatment resistance strains. Although current research has provided significant insight into TB transmission, diagnosis, and treatment in the last four years, much more progress is needed to successfully reduce tuberculosis prevalence and eventually eradicate it. The disease continues to be a public health concern, second only to HIV/AIDS in high fatality rates. This review focuses on current efforts to translate the anti-tubercular activity of all known pyrazinamide analogues and proposes a novel approach for developing new anti-tubercular drugs based on the fusion of pyrazinamide with various heterocyclic rings that shorten treatment for drug-sensitive and multidrug-resistant tuberculosis.

Long non-coding RNA has attracted the interest of researchers as a relevant factor that can influence human cancers. As an oncogene and suppressor gene, it has numerous pathways and is closely related to the pathophysiology of human diseases. Meanwhile, it may become a novel treatment option and target for tumor treatment. CRNDE is the gene symbol for Colorectal Neoplasia Differentially Expressed (non-protein-coding) since it was found to be considerably higher in colorectal cancer when it was first discovered. It's transcribed from human chromosome 16. Many studies have shown that it is intimately linked to the etiology of many tumors and malignancies. According to the paper, the biological function and pathophysiological mechanism of CRNDE in tumors have been studied extensively in recent years. PubMed served as an essential platform for conducting literature searches and related analyses. CRNDE, a long non-coding RNA closely related to tumors, was highly expressed in many tumor cells. There were various underlying mechanisms affecting the progression of CRNDE-regulated tumorigenesis, including hepatocellular carcinoma, gastric cancer, prostate carcinoma, oral squamous cell carcinoma, breast cancer, thyroid cancer, myeloma, leukemia, melanoma, colorectal cancer, glioblastoma, osteosarcoma, cervical cancer, intrahepatic cholangiocarcinoma, nonsmall cell lung cancer, hepatoblastoma cell tumor, abdominal aortic aneurysm, nasopharyngeal carcinoma, bladder cancer, Wilms tumor, medulloblastoma, pancreatic cancer, gallbladder cancer, ovarian cancer, and renal cell carcinoma. CRNDE is involved in the processes of proliferation, migration, invasion, and inhibition of apoptosis of various cancer cells.

Nanotechnology has been widely studied in biomedical applications in the last decade. The revolution in nanotechnology triggers the fabrication of nanomaterials with novel properties and functionalities, making the research in nanosensors and biomedical rapidly expanding. Nanosensor application has improved the sensitivity by enhancing their catalytic activity, conductivity, and biocompatibility. Calixarene is excellent as a sensing element used as a sensor due to its unique host-guest properties. Three major types of calixarene which are extensively studied are calix[4]arene, calix[6]arene, and calix[8]arene. These organic nanomaterials resemble vase-like supramolecular structures and exhibit valuable properties. Calixarene's basic molecular design is the cyclic phenol tetramer with four aryl groups, perfect for molecular recognition such as cations, transition metal ions, and heavy metals. Calixarenes may form stable complexes with biomolecules in developing biosensors for protein, enzyme, and antibody sensing. Calixarene's lower rim can be modified for optimum molecular interaction with guest molecules such as anions, cations, and neutral molecules. The lower ring has welldefined conformation properties and cavities, which allow trapping guest drugs such as imatinib, paclitaxel, and temozolomide. Calixarene also possesses good biocompatibility and innocuousness and gained attention for cancer treatment due to the response to multiple stimuli, stability, avoiding non-specific cell uptake, and reaching the target for treatment effect. This review paper focuses on the synthesis and characteristics of calixarene applied in nanosensors as an ideal complex agent in drug transportation and controlled drug released for biomedical research.

Background: Chlamydia trachomatis infection is one of the most common sexually transmitted diseases. There is widespread evidence in recent years that indicate C. trachomatis infection plays a role in sperm dysfunction and poor sperm quality. However, some controversial documents have argued the role of infection with this bacterium in male infertility. Methods: A full comprehensive electronic search was performed using the online databases Web of Science, PubMed, Scopus, Embase, and Google Scholar, without considering the time limits. Results: In the present study, 56 articles were finally found to be eligible. The prevalence of C. trachomatis infection in the infertile males was estimated at 20.6% (19.8-21.5 with 95% CIs; p- Value: 0.01; I2: 97.77; Q-Value: 237.8; p-Value: 0.01; Begg's p-Value: 0.09; Egger's p-Value: 0.01) in overall. We have also shown that infection with C. trachomatis can significantly increase the risk of infertility in men (OR: 2.28; 1.90-2.72 with 95% CIs; p-Value: 0.001; I2: 81.61; QValue: 59.81; p-Value: 0.01; Begg's p-Value: 0.73; Egger's p-Value: 0.61). Conclusion: We showed a high prevalence of C. trachomatis in the sperm and semen samples of infertile men, and C. trachomatis infection is associated with a significantly higher risk of infertility in men.

Background: Neurodegenerative Diseases (NDs) are characterized by progressive neuronal deterioration as a result of several pathogenesis mechanisms. Phytochemicals, including sesamin with multitarget activities, have been studied widely. Objective: In this review, we aim to survey the neuroprotective effects of sesamin on NDs and its mechanisms of action. Methods: Searching GoogleScholar, PubMed, and Science Direct databases, we reviewed original English language articles on sesamin effects against NDs, specifically Alzheimer’s Disease (AD) and Parkinson's Disease (PD), either in vivo or in vitro settings, with no time limitation. Results: Sesamin has been reported to interfere with NDs progression through its antioxidative, antiinflammatory, and antiapoptotic actions in most of the retrieved studies. Sesamin also can prevent amyloid-β aggregation in AD models and elevate dopamine levels in PD-induced models. Conclusion: The results of this study revealed the beneficial effects of sesamin in the prevention and management of NDs, including AD and PD; however, no clinical data supporting these effects in humans is available, which highlights the need for designing clinical trials to evaluate the efficacy, proper dosage, pharmacokinetics aspects, and possible side effects of sesamin in humans.