Current topics in medicinal chemistry最新文献

Visible-light-mediated reactions have recently emerged as a powerful strategy for the synthesis of diverse organic molecules under mild reaction conditions. Usually, the reactions are performed at room temperature and thus sensitive functional groups remain unaffected. Thus, this protocol has received intense interest from academia as well as industries. The heterocycles, in general, are of much interest because of their biological activities and application in therapeutics. The Oxygen- and Sulfur-containing heterocyclic compounds have recently attracted attention as these compounds showed promising activities as anti-cancer drugs, antibiotics, antifungal and anti-inflammatory agents among other applications. The synthesis of this class of compounds by efficient and greener routes has become an important target. This review highlights the various procedures for the synthesis of these compounds and their derivatives under visible light-induced reactions. The green aspects and mechanism of each procedure have been discussed.

For many centuries, traditional medicine has played an essential role in health care. The treatment of many illnesses, including cancer, has greatly benefited from using herbal remedies derived from traditional medicine. The bioactive compounds, such as curcumin, silibinin, berberine, ginseng, and others present in traditional medicine have shown a wide range of properties, such as anti-inflammatory, antimicrobial, anti-oxidant as well as potent anti-cancer properties both in laboratory studies and animal experiments (in vitro and in vivo). In this review, we mainly emphasized the anticancer role of bioactive compounds present in traditional medicine, such as curcumin, cardamonin, piperine, berberine, ginseng, silibinin, epigallocatechin gallate, and asafoetida. We also discussed molecular evidence of these compounds in chemoprevention and anticancer effects. These compounds have the potential to interfere with cancer growth, proliferation, metastasis, and angiogenesis and induce apoptosis by targeting different pathways and the cell cycle. This review article also focuses on how these compounds can help overcome drug resistance and enhance the availability of other clinically approved drugs. The usage of these compounds synergistically with other forms of treatment is also of great fascination to new and upcoming research. Finally, we have discussed the bioavailability of these compounds and strategies employed to improve them so their full potential can be exploited.

Osteoarthritis (OA) is a common chronic articular degenerative disease characterized by articular cartilage degradation, synovial inflammation/immunity, and subchondral bone lesions. Recently, increasing interest has been devoted to treating or preventing OA with herbal medicines. The mechanism of action of plant raw materials used in osteoarthrosis treatment is well documented. They are sought after because of the high frequency of inflammation of the knee joint among both elderly and young people engaged in sports in which their knee joints are often exposed to high-stress conditions. The purpose of this work was to present some most effective and safe plant medicines with proven mechanisms of action that can help to alleviate the growing social problem of osteoarthrosis caused in recent years. A review of the available literature based primarily on the latest editions of ESCOP and EMA monographs and the latest scientific papers has made it possible to select and propose medical management of osteoarthrosis by ranking plant medicines according to their effectiveness. Clinical studies of raw plant materials, such as Harpagophyti radix, Olibanum indicum, and Urticae foliumet herba have indicated that these drugs should be considered the first choice in osteoarthrosis treatment. The efficacy of Rosae pseudo-fructus, Salicis cortex, Filipendulae ulmariae flos et herba, Ribis nigri folium, and externally applied Capsici fructus and Symphyti radix, has also been proven by pharmacological studies. All the plant medicines mentioned in the paper have been studied in detail in terms of their phytochemistry, which can help doctors in their decision-- making in the treatment of osteoarthrosis.

Alzheimer's Disease (AD) is a serious neurological illness that causes memory loss gradually by destroying brain cells. This deadly brain illness primarily strikes the elderly, impairing their cognitive and bodily abilities until brain shrinkage occurs. Modern techniques are required for an accurate diagnosis of AD. Machine learning has gained attraction in the medical field as a means of determining a person's risk of developing AD in its early stages. One of the most advanced soft computing neural network-based Deep Learning (DL) methodologies has garnered significant interest among researchers in automating early-stage AD diagnosis. Hence, a comprehensive review is necessary to gain insights into DL techniques for the advancement of more effective methods for diagnosing AD. This review explores multiple biomarkers associated with Alzheimer's Disease (AD) and various DL methodologies, including Deep Neural Networks (DNN), Convolutional Neural Networks (CNN), Recurrent Neural Networks (RNN), The k-nearest-neighbor (k-NN), Deep Boltzmann Machines (DBM), and Deep Belief Networks (DBN), which have been employed for automating the early diagnosis of AD. Moreover, the unique contributions of this review include the classification of ATN biomarkers for Alzheimer's Disease (AD), systemic description of diverse DL algorithms for early AD assessment, along with a discussion of widely utilized online datasets such as ADNI, OASIS, etc. Additionally, this review provides perspectives on future trends derived from critical evaluation of each variant of DL techniques across different modalities, dataset sources, AUC values, and accuracies.

Flavonoids belong to the polyphenol group that naturally exists in fruits, vegetables, tea, and grains. Flavonoids, as secondary metabolites, show indispensable contributions to biolog-ical processes and the responses of plants to numerous environmental factors. The bioactivity of flavonoids depends on C6-C3-C6 ring substitution patterns that exhibit bioactive antioxidant, an-timicrobial, antifungal, antitumor, and anti-inflammatory properties. The synthesis of flavonoids has been reported by various methodologies. Therefore, the present review systematically sum-marizes the synthesis of recent heterocyclic flavonoid derivatives via facile synthetic approaches since the research in flavonoids is useful for therapeutic and biotechnology fields.

Circadian rhythms of innate 24 h cycles comprise well-conserved biological phenomena from cyanobacteria to mammalian. They are driven by light and regulated by clock genes that work as transcription factors and control the expression of many other genes and physiological functions in the cells. The expression of ~ 40% of protein-coding genes shows 24 h oscillation patterns in mice, implying their importance in normal body functions. Indeed, the physiological and behavioural rhythmicity generated through clock genes-mediated multiple mechanisms affects the quality of life at large. Disrupted circadian rhythmicity is associated with several kinds of diseases. For example, cancer cells show abnormal expression patterns for circadian rhythm genes that have been shown to regulate oncogenesis, drug responses, and disease prognosis. Furthermore, the modern globalisation of human lifestyle and business and social activities have disrupted innate circadian rhythm, resulting in a variety of diseases through disrupted humoral, immunological, and neuronal pathways. Safe and sustainable modulation of circadian rhythm has become a prevalent need that warrants basic and interventional research, as well as clinical investigations. Although traditional systems of medicine suggest some natural compounds with circadian rhythmmodulating potential, most of these have not been validated in laboratory or clinical studies. Reliable read-outs of the effects of test compounds on circadian rhythmicity have been limited by the availability of live cell assays. We have, herein, provided an overview of living cell-embedded real- time reporter gene assays designed for screening compounds that modulate circadian rhythm, and discussed the potential of some natural compounds for circadian rhythm modulation as validated by cell-based assay systems, and their role in disease therapeutics.

In recent years, mesenchymal stem cells (MSCs) have emerged as promising anti-- cancer mediators with the potential to treat several cancers. MSCs have been modified to produce anti-proliferative, pro-apoptotic, and anti-angiogenic molecules that could be effective against a variety of malignancies. Additionally, customizing MSCs with cytokines that stimulate pro-tumorigenic immunity or using them as vehicles for traditional chemical molecules with anti-cancer characteristics. Even though the specific function of MSCs in tumors is still challenged, promising outcomes from preclinical investigations of MSC-based gene therapy for a variety of cancers inspire the beginning of clinical trials. In addition, the tumor microenvironment (TME) could have a substantial influence on normal tissue stem cells, which can affect the treatment outcomes. To overcome the complications of TME in cancer development, MSCs could provide some signs of hope for converting TME into unequivocal therapeutic tools. Hence, this review focuses on engineered MSCs (En-MSCs) as a promising approach to overcoming the complications of TME.

Background: Humic acid (HA) is a bioproduct that can be extracted from different sources and has anti-inflammatory properties that have been little explored in the treatment and prevention of Periodontal Disease (PD). Thus, we aimed to investigate the effects of oral administration of HA on the progression of PD in rats.

Methods: Twenty-four male Wistar rats were distributed into three experimental groups (Control/ Sham, PD, and PD + HA). HA was administered by gavage (80 mg/kg/day) for 28 days, and PD was induced 14 days after the beginning of treatment. Bone loss, bone topography, and surface elemental composition were analyzed. Circulating IL1-beta, TNF-alpha, and IL-10 levels were evaluated through Enzyme-Linked Immunosorbent Assay (ELISA).

Results: The animals treated with HA showed lower bone loss (p < 0.05). Calcium and phosphorus levels on the alveolar bone surface were lower in the PD group (p < 0.05) compared to the control group, whereas the animals treated with HA exhibited attenuation in this loss (p < 0.05). The animals treated with HA showed reduced TNF-alpha, IL1-beta, IL-10, and the TNF-alpha/IL-10 ratio compared to those with PD (p < 0.05).

Conclusion: Treatment with HA attenuated the parameters of alveolar bone loss and modulated systemic inflammatory parameters in rats with ligature-induced PD.