Mini Reviews in Medicinal Chemistry - Volume 21, Issue 6, 2021

The cholinergic anti-inflammatory pathway is a part of the parasympathetic nervous system and it can also be entitled as an anti-inflammatory reflex. It consists of terminations of the vagal nerve into blood, acetylcholine released from the terminations, macrophages and other cells having α7 nicotinic acetylcholine receptor (α7 nAChR), calcium ions crossing through the receptor and interacting with nuclear factors, and erythrocytes with acetylcholinesterase (AChE) terminating the neurotransmission. Stopping of inflammatory cytokines production is the major task for the cholinergic antiinflammatory pathway. The cholinergic anti-inflammatory pathway can be stimulated or suppressed by agonizing or antagonizing α7 nAChR or by inhibition of AChE. This review is focused on cholinergic anti-inflammatory pathway regulation by drugs. Compounds that inhibit cholinesterases (for instance, huperzine, rivastigmine, galantamine), and their impact on the cholinergic anti-inflammatory pathway are discussed here and a survey of actual literature is provided.

Cardiovascular diseases and fatty liver disease have become the leading causes of death in modern society. However, the currently existing drugs do not solve all issues related to these diseases; thus, it is expected that more potential drugs for clinical use will be developed. Undeniably, natural products have attracted increasing attention. It is of great significance to identify effective active monomer components for drug discovery and disease prevention. As a pure natural product, Agathis dammara (AD) has antioxidant, hypolipidemic, hypoglycemic, antitumor, and anti-inflammatory activities. However, at present, there are few reports regarding the effects of AD on chronic inflammatory cardiovascular diseases, such as aneurysm, atherosclerosis, myocardial ischemia-reperfusion injury, and cardiac hypertrophy and liver diseases such as fatty liver disease. AD and products derived from it have a very broad application prospect for cardiovascular diseases and fatty liver disease.

According to statistics, cancer is the second leading cause of death in the world. Thus, it is important to solve this medical and social problem by developing new effective methods for cancer treatment. An alternative to more well-known approaches, such as radiotherapy and chemotherapy, is photodynamic therapy (PDT), which is limited to the shallow tissue penetration (< 1 cm) of visible light. Since the PDT process can be initiated in deep tissues by X-ray irradiation (X-ray induced PDT, or XPDT), it has a great potential to treat tumors in internal organs. The article discusses the principles of therapies. The main focus is on various nanoparticles used with or without photosensitizers, which allow the conversion of X-ray irradiation into UV-visible light. Much attention is given to the synthesis of nanoparticles and analysis of their characteristics, such as size and spectral features. The results of in vitro and in vivo experiments are also discussed.

Background: COVID-19 has become a pandemic with higher morbidity and mortality rates after its start from Wuhan city of China. The infection by RNA virus, also known as SARS-CoV-2 or 2019-nCoV, from the beta class of coronaviruses, has been found to be responsible for COVID-19. Structural analysis and evidences have been indicated that interaction between a segment of receptor binding domain (RBD) from S protein of the virus and human angiotensin-converting enzyme 2 (hACE2) is essential for cellular entry of the virus. Objective: The current review sheds light on structural aspects for the inhibition of RBD-hACE2 interaction mediated cellular entry of SARS-CoV-2. Methods: The present study provides a critical review of recently published information on RBDhACE2 interaction and its inhibitors to control SARS-CoV-2 infection. The review highlighted the structural aspects of the interaction between RBD-hACE2 and involved amino acid residues. Results: Recently, several studies are being conducted for the inhibition of the SARS-CoV-2 attachment and entry to the human cellular system. One of the important targets for viral invasion is its binding with cell surface receptor, hACE2, through RBD on S-protein. Mimicking of three residues on ACE2 (Lys31, Glu35 and Lys353 on B chain) provided a hot target directed strategy for the inhibition of early attachment of the virus to the cell. Early screening of peptidic or non-peptidic molecules for the inhibition of RBD-hACE2 interaction has raised the hope for potential therapeutics against COVID-19. The higher affinity of molecules toward RBD than ACE2 is an important factor for selectivity and minimization of ACE2 related adverse events on the cardiovascular system, brain, kidney, and foetus development during pregnancy. Conclusion: Inhibition of RBD-hACE2 interaction by different molecular scaffolds can be used as a preferred strategy for control of SARS-CoV-2 infection. Recently, published reports pointed out Lys31, Glu35 and Lys353 on the B chain of ACE2 as crucial residues for mimicking and design of novel molecules as inhibitors SARS-CoV-2 attachment to human cells. Moreover, some recently identified RBD-hACE2 interaction inhibitors have also been described with their protein binding pattern and potencies (IC50 values), which will help for further improvement in the selectivity.

The current pandemic of COVID-19 caused by SARS-Cov-2 has posed a severe threat to the whole world with its highly infectious, progressive nature with up to 10% mortality rates. The severity of the situation faced by the whole world and the lack of efficient therapeutics to treat this viral disease have led the WHO to depend on the drug-repurposing approach to tackle this major global health problem. This review aims at highlighting the various synthetic approaches employed for the synthesis of these FDA approved drugs that have been presently used for COVID-19 treatment. Additionally, a brief overview of several therapeutic strategies is also presented. This review will encourage the scientific community across the globe to come up with better and efficient synthetic protocols and also novel chemical entities along with this core with more potent activity.

Fenugreek (Trigonella foenum-graecum L.) is a native plant found in the parts of Iran to the North of India, and is presently planted also in other regions of the world. Fenugreek is considered a notable multipurpose medicinal and traditional herb in Iran, India, and China for several centuries. The most important components of fenugreek seeds are protein, neutral detergent fiber, gum, lipids, moisture, ash and starch. Fenugreek seeds and leaves are anti-cholesterolemic, anti-tumor, antiinflammatory, carminative, demulcent, deobstruent, emollient, expectorant, galactogogue, febrifuge, laxative, hypoglycaemic, restorative, parasiticide and uterine tonic and useful in burning sensation. Traditionally, fenugreek seeds being used worldwide are beneficial for bone and muscles, respiratory system, gastro-intestinal system, female reproductive system, cardio-vascular system, endocrinology and hepatic. Fenugreek helps reduce cholesterol, reduce cardiovascular risk, control diabetes, a good consolation for sore throats, a remedy for acid reflux, constipation, colon cancer prevention, appropriate for kidney trouble, skin infection, increase milk production, reduce menstrual discomfort, and reduce menopause symptoms. It is also an appetite suppressant that helps in weight loss. Both modern science and traditional medicine integration with novel technologies and discoveries will secure the cultivation of medicinal herbs and promote sustainability in the long-term and a wide-range.

Cancer is a deadly disease, which has significantly increased in both developed and developing nations. Treatment of cancer utilizing radiotherapy or chemotherapy actuates a few issues which incorporate spewing, sickness, unpalatable reactions, and so forth. In this specific situation, an alternative drug source, which can effectively treat cancer is of prime importance. Products that are obtained from plant sources are utilized for the treatment of various diseases due to their non-harmful nature. Medicinal plants contain different bioactive compounds, which possess an important role in the prevention of different diseases such as cancer. Plumbagin is a bioactive compound, which is mainly present in Plumbaginaceae family and has been explored for its anticancer activity. Plumbagin basically inactivates the Akt/NF-kB, MMP-9 and VEGF pathways that are essential for cancer cell development. Therefore, it is important to review the role of plumbagin in different cancer cells in order to find an alternative drug to overcome this disease. The present review provides a summary of anticancer activity of plumbagin in various cancers and its mode of action.

After the clinical use of epalrestat that contains a rhodanine ring, in type II diabetes mellitus and diabetic complications, rhodanin-based compounds have become an important class of heterocyclic in the field of medicinal chemistry. Various modifications to the rhodanine ring have led to a broad spectrum of biological activity of these compounds. Synthesis of rhodanine derivatives, depended on advenced throughput scanning hits, frequently causes potent and selective modulators of targeted enzymes or receptors, which apply their pharmacological activities through different mechanisms of action. Rhodanine-based compounds will likely stay a privileged scaffold in drug discovery because of different probability of chemical modifications of the rhodanine ring. We have, therefore reviewed their biological activities and structure activity relationship.