Mini Reviews in Medicinal Chemistry - Volume 21, Issue 15, 2021

In recent years, marine-derived Penicillium fungi have received remarkable interest as a valuable source of novel natural products encompassing diverse chemical structures and bioactive properties. Mangroves, sediments, algae, and sponges are the four main sources of marine-derived Penicillium fungi. As of 2014, more than 390 novel natural products have been isolated from the marine- derived Penicillium fungi, mainly including polyketides, alkaloids, terpenoids, and macrolides. Biological investigations have shown that these compounds possess antimicrobial, anti-inflammatory, cytotoxic, and other activities with potential applications in new drug development. To provide an updated catalog of this field, our mini-review summarized the origins, structures, and bioactivities of 188 secondary metabolites from marine-derived Penicillium fungi based on bioactivities classification published from 2015 to 2020.

Oleanolic acid can inhibit edema and exhibit obvious inhibitory activity to inflammatory by activating of the pituitary-adrenal cortical system, inhibiting the synthesis or release of PGs, inhibiting endotoxin-mediated release of HMGB1 by endothelial cells or regulating MAPK, PI3K/Akt/NF- ΚB/ICAM-1/JAK/STAT signaling pathways, etc. In recent years, an increased number of interesting research work has been carried out on the anti-inflammatory activity and mechanisms of OA derivatives, such as acyloxyimino derivative, 3-acetylated derivatives, novel 3,5-disubstituted isoxazoles derivatives, acetate, ester derivatives and oximes derivatives. The review summaries and highlights the updated advances on the anti-inflammatory activity and mechanism of OA and its derivatives.

Alzheimer's disease (AD) is a progressive neurodegenerative disease with concealed onset, which is characterized by the damage of the cholinergic system, deposition, and accumulation of β- amyloid protein (Aβ) and neurofibrillary tangles. Because the cholinergic system plays a key role in the process of brain memory, it has become one of the important targets in anti-AD research. In view of the complicated pathological characteristics of AD, the multi-target directed ligands (MTDLs) that can act on multiple targets are considered to be an effective treatment strategy at present. Tacrine, as the first acetylcholinesterase (AChE) inhibitor, has been discontinued because of its hepatotoxicity, but its core structure is simple and easy to modify. By using tacrine to target the active catalytic site (CAS), the tacrine-based MTDLs can act on both CAS and peripheral anion site (PAS) of AChE to serve as a dual-site AChE inhibitor. Additionally, the tacrine-based MTDLs can also be designed on the basis of other theories of AD, for example, introducing functional moieties to modulate the formation of β-amyloid (Aβ), oxidation resistance, or metal chelation. In this paper, the research progress of tacrine-based MTDLs is summarized.

Non-steroidal anti-inflammatory drugs (NSAIDs) are agents that are used for various properties such as analgesic activity, anti-inflammatory activity, antipyretic activity, etc. But this class of drugs is associated with different side effects such as dyspepsia, gastroduodenal ulcers, gastrointestinal (GI) bleeding and perforation. The prodrug approach is quite beneficial to curb these side effects. Prodrugs are the inactive compounds that, on metabolism get converted into an active metabolite exhibiting desired activities. Commonly used approaches for synthesizing prodrugs are amide, esters, and mutual prodrugs by suppressing the free carboxylic groups responsible for these side effects. In this review, different schemes reported for the synthesis of NSAIDs that are devoid of undesired side effects such as irritation to gastric mucosa, gastrotoxicity, and ulcerogenicity have been compiled. Docking studies and the structure-activity relationship of some compounds are also discussed. The paper shall help the researchers to understand the methods to expedite the synthesis by carrying out substitutions of various groups of the parent compound and establish the mechanism of action of these derivatives of masking the unwanted side effects.

Background: The most documented illness affecting women overall is breast malignant growth. Since breast cancer disease is the most widely recognized threat in women, Since breast cancer disease is the most widely recognized threat in women, this review was done to provide data on the ongoing advancements in the medication focused on in the breast cancer regimen. Over the previous decades, it has been seen that different progressions have been made in the disclosure of new medications and treatments for treating breast malignancy and this is a direct result of the improved comprehension of the biologic heterogeneity of breast cancer, which has likewise permitted the advancement of increasingly compelling ways to deal with treating breast cancer. Methods: We searched the scientific database using relevant keywords. Among the searched literature, only peer-reviewed papers were collected, which address our questions. The retrieved quality papers were screened and analyzed critically. The key findings of these studies are included along with the importance. Results: The research in this review particularly includes the anti-breast cancer drugs, which accountfor the top largest market by sales in the pharmaceutical industry. Apart from these, natural and innovative therapies have emerged leading to better management of breast cancer. Conclusion: These recent developments have contributed to a more efficient and specific treatment protocol in breast cancer patients. Moreover, further investigation should be done in improving results for all the patients with breast cancer disease, particularly individuals who have advanced breast cancer and the issue of drug resistance, which also poses a threat to the successful development of targeted therapy in various subtypes of breast cancer, must also be considered.

Acrylic resins are the most commonly used materials in prosthetics and orthodontics until now. They have a well-documented history of use as biomaterials in the manufacturing of different types of dental appliances. The objective of this study was to describe the properties of acrylic resins and the processing methods used for these materials in dentistry. The review depicts the most important achievements in this area, indicating that the resin technology evolved in different directions. The mechanical and biological properties of acrylic resins were improved by the addition of mineral or natural fibers, and/or fillers, including nanofillers, as well as by poly(methyl methacrylate) surface modification. The presence of residual monomer was reduced as a result of postpolymerization activity. New types of acrylic resins were developed for processing Computer-Aided Design/Computer- Aided Manufacturing systems and three-dimensional printing.

Over the years, the development of bioactive heterocycles has aroused the interest of the scientific community, because in general, these heterocycles are strategic in maintaining life. Research into bioactive heterocycles is associated with the development of methods of synthesis and the biological evaluation of different nuclei. In consequence, there has been a growing interest in the nucleus of fused pyrimidine, which has diversified pharmacological activities, including diuretic, antimicrobial, antifolate, tyrosine kinase, anti-inflammatory, anticancer, anthelminthic, and antiviral activities. This review focuses on describing a diverse set of structures derived from pyrimido[4,5-d]pyrimidines and contemplates the main bioactivities of these nuclei.

Galectin-1 (Gal-1), a 14kDa carbohydrate-binding protein of the galectin family found in humans, affects intracellular signaling pathways upon interaction with β-galactosides on cell-surface, cytosol, and nucleus. The structural information reveals that it consists of a monovalent dimer composed of subunits with one Carbohydrate Recognition Domain (CRD), which is the main active site to interact with various glycoproteins, and carbohydrates in the body to regulate cellular functions. Gal-1 contributes towards different events associated with cancer biology, including tumor transformation, cell cycle regulation, apoptosis, cell adhesion, migration, and inflammation. The extracellular existence and function of Gal-1 have been well-established, and it is known to express in many tumor types, including astrocytoma, melanoma, prostate, colon, bladder, and ovarian carcinomas, etc. Several studies suggested the upregulation of Gal-1 levels in multiple cancer cells. Thus, Gal-1 is a promising molecular target for the development of new therapeutic tools. The present review focuses on the functions of Gal-1 in tumor progression in multiple cancers and its structural insights.

P-Coumaric acid (p-CA) is a hydroxycinnamic acid, an organic compound that is a hydroxyl derivative of cinnamic acid. P-CA is the most abundant isomer in nature and can be found in a wide variety of edible plants such as fungi, peanuts, navy beans, tomatoes, carrots, basil, and garlic. Recently, the therapeutic properties of p-CA have received a great deal of attention from scientific society. Here, we described the medicinal effects of p-CA on various pathological conditions. This review was performed via evaluating PubMed reported studies from January 2010 to January 2020. Also, reference lists were checked to find additional studies. All intermediation or complementarity of animal models, case-control and cohort studies, in vitro studies, and controlled trials (CTs) on p-CA were acceptable. However plant extract studies without indication of main active substances were excluded due to the considerable diversities and heterogeneities. According to recent evidence regarding the beneficial effects of p-CA, numerous diseases such as nephropathies, cardiovascular diseases, neuroinflammatory diseases, liver diseases, cancers, and some metabolic disorders could potentially be controlled by this natural herb. Interestingly, autophagy is a novel molecular mechanism involved in the crosstalk between classic effects of p-CA and introduces alternative therapeutic pathways for this compound. Much work remains in clarifying the main therapeutic properties among the various p-CA effects; these will be the subject of forthcoming work, resulting in presenting further mechanism of action.