Mini Reviews in Medicinal Chemistry - Volume 23, Issue 4, 2023

Alzheimer’s Disease (AD) is a common neurodegenerative disorder that is almost incurable with the existing therapeutic interventions. Due to the high-risk factors associated with this disease, there is a global pursuit of new anti-AD agents. Herein, we explore the biochemical pathways which are responsible for the initiation/propagation of the disease. It is observed that out of the two isoforms of β-secretase, β-site amyloid precursor protein cleaving enzyme 1 (BACE1) and β-site amyloid precursor protein cleaving enzyme 2 (BACE2) present in the brain, BACE1 plays the predominant role in the commencement of AD. Moreover, the catalytic activities of acetylcholinesterase and butyrylcholinesterase regulate the concentration of neurotransmitters, and they are needed to be kept under control during the signs of AD. Hence, these two enzymes also serve as potential targets for the treatment of AD patients. Keeping in view the multifactorial nature of the disease, we also reviewed the multitarget approach for the treatment of AD. It is tried to identify the common structural features of those molecules which act on different cellular targets during AD therapy.

The self-assembly behavior of polypeptides is common in nature. Compared with monopeptides, polypeptide-based self-assembled nanomaterials with ordered structures have good thermal stability, mechanical stability, semi-conductivity, piezoelectric and optical properties. In recent years, the self-assembly of polypeptides has become a hot topic in the material science and biomedical field. By reasonably adjusting the molecular structure of the polypeptide and changing the external environment of the polypeptide, the polypeptide can be self-assembled or triggered by non-covalent bonding forces such as hydrogen bond, hydrophobicity, and π - π accumulation to form specific polypeptide assemblies such as nanoparticles, hydrogels, nanofibers, and micelles. Due to good biocompatibility and controllable degradability, polypeptide-based self-assembled nanomaterials have been widely used in the fields of nanotechnology, imaging technology, biosensor, and biomedical science. As a new drug delivery system, the polypeptide-drug conjugate has the advantages of low toxicity, high efficiency, enhanced drug stability, and avoiding side effects. This paper reviews the research progress of polypeptide-drug self-assembly nanostructure in recent years. Several structural models of polypeptide self-assembly technology and the mechanism of polypeptide self-assembly are introduced. Then the assembly form of polypeptide-drug self-assembly and the application of selfassembly compound therapy is described.

Breast cancer is the most frequently diagnosed and leading cause of cancer-related deaths in women worldwide. Based on global cancer (GLOBOCAN) 2020 statistics, 1 in 4 cancer cases and 1 in 6 cancer deaths are attributable to breast cancer, leading both in incidence and mortality. To address the increasing burden of cancer, novel therapeutic approaches that target key hallmarks of cancer are explored in cancer drug discovery. Cyclin-dependent kinase (CDK) inhibitors are generally purine and pyrimidine analogues validated for the treatment of cancer due to their unique roles in cancer deregulation and novel therapeutic potentials. So far, three orally administered, potent and highly selective CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) have been approved by the FDA for the targeted treatment of advanced or metastatic breast cancer in combination with endocrine therapy. Furthermore, several compounds derived from various synthetic scaffolds are being explored with promising results and positive outcomes in various stages of clinical trials. In this review, we highlight these CDK4/6 inhibitor compounds with potent anti-CDK4/6, in vitro and in vivo activities on breast cancer cells. With the remarkable prospects of these compounds, there is great optimism further novel CDK inhibitor compounds will be discovered in the future that could boost therapeutic options for cancer treatment.

Centrosome abnormalities are the hallmark of cancer. How it affects tumorigenesis is still a mystery. However, the presence of more than two centrosomes at the onset of mitosis often leads to chromosomal instability and subsequent tumorigenesis. Unlike normal cells that undergo repair or apoptosis in response to this instability, cancer cells learn to cope with supernumerary centrosomes through various mechanisms and survive. Centrosome clustering is the most prevalent mechanism, allowing the cancer cells to form two daughter cells through a pseudo-bipolar spindle. Since healthy cells are devoid of the mechanisms involved in clustering, the de-clustering of centrosomes can be considered a promising approach to selectively eliminate cells with extra centrosomes. Several proteins such as PARP, KIFC1, Hsp70, Cortical actin, APC/C-CDH1 complex and Eg5 have been discussed in this review which participate in centrosome clustering, and the inhibition of these proteins can facilitate in impeding tumor growth specifically by declustering centrosomes. In this review, we also present the role of the centrosome in the cell cycle, centrosome amplification, clustering mechanism and reported centrosome de-clustering agents to present the current state of work in the field.

Background: Liver disease rates are gradually increasing over the years, becoming a severe public health problem. The indiscriminate use of drugs associated with a rich fat diet, high consumption of alcoholic beverages, and exposure to viral infections and lipid peroxidative products are considered the chief factors for developing hepatic disorders. Owing to the absence of reliable hepatoprotective drugs in the therapeutic arsenal, since they present a high incidence of adverse reactions and/or lack of efficacy in some cases, liver diseases are widely treated with medicinal plants. Among them are the plants producing iridoids, which are believed to be good remedies for liver disease due to their bitter taste. The hepatoprotective effect of iridoids and extracts, rich in these compounds, has been demonstrated, both in vitro and in vivo. Objective: This review aims to scrutinize the available literature related to the hepatoprotective activity of iridoids. Methods: The information was obtained from scientific databases (Science Direct, PubMed, Web of Science, Scopus, ACS Publications, Wiley Online Library) until December, 2021. Results and Conclusion: A total of 63 hepatoprotective iridoids were found, including aucubin, catalpol and picroliv, a mixture of two iridoids. They are the target of a high number of studies, which revealed their protective action against different hepatotoxic agents and detailed action mechanisms.

Molecular biology is a widely used and widespread technique in research and as a laboratory diagnostic tool, aiming to investigate targets of interest from the obtainment, identification, and analysis of genetic material. In this context, methods, such as Polymerase Chain Reaction (PCR), Reverse Transcription Polymerase Chain Reaction (RT-PCR), real-time PCR, loopmediated isothermal amplification (LAMP), and loop-mediated isothermal amplification with reverse transcription (RT-LAMP), can be cited. Such methods use enzymes, buffers, and thermosensitive reagents, which require specific storage conditions. In an attempt to solve this problem, the lyophilization procedure (dehydration process by sublimation) can be applied, aiming to preserve and prolong the useful life of the reaction components in cases of temperature variation. In this review, we present a synthesis of the lyophilization process, describing the events of each step of the procedure and providing general information about the technique. Moreover, we selected lyophilization protocols found in the literature, paying attention to the conditions chosen by the authors for each step of the procedure, and structured the main data in tables, facilitating access to information for researchers who need material to produce new functional protocols.

Leprosy is a Neglected Tropical Disease (NTDs) caused by Mycobacterium leprae (M. leprae). The treatment is considered effective, however, the high dose Multidrug Therapy (MDT) for a long period and its adverse effects result in the abandonment of the treatment by patients. Indeed, antimicrobial resistance is still an obstacle that must be overcome in the treatment of leprosy. In the present article, we reviewed the WHO guidelines for the chemotherapy of leprosy and the methods of synthesis of these drugs.