Mini Reviews in Medicinal Chemistry - Volume 21, Issue 16, 2021

COVID-19 is an emerging viral infection of zoonotic origin that is closely related to the severe acute respiratory syndrome coronavirus (SARS-CoV) that caused an outbreak in 2003. Therefore, scientists named the new virus SARS-CoV-2. On March 11, 2020, The World Health Organization (WHO) recognized COVID-19 as a global pandemic. At present, three vaccines have been approved or are being considered for approval by national regulatory agencies to immunize against COVID- 19. However, the vaccines do not remain widely available, and no specific treatment against the virus is available. The pathogenesis and proliferation pathways of SARS-CoV-2 are still not well known. Thus, in this article, the saponin glycyrrhizin is discussed as a new potential therapeutic agent of natural origin (licorice root, Glycyrrhiza glabra) for the potential treatment of COVID-19 infections.

Quinoline and its derivatives comprise an important group of heterocyclic compounds that exhibits a wide range of pharmacological properties such as antibacterial, antiviral, anticancer, antiparasitic, anti-Alzheimer and anticholesterol. The quinoline nucleus is found in the structure of many drugs and rational design in medicinal chemistry for the discovery of novel bioactive molecules. Persistent efforts have been made over the years to develop novel congeners with superior biological activities and minimal potential for undesirable side effects. This review highlights some discoveries on the development of quinoline-based compounds in recent years (2013-2019), focusing on their biological activities, including anticancer, antitubercular, antimalarial, anti-ZIKV, anti-DENV, anti- Leishmania and anti-Alzheimer’s disease.

The development of new drugs is becoming notably harder each decade. To overcome the present pitfalls in the drug development pipeline, such as those related to potency, selectivity, or absorption, distribution, metabolism, excretion and toxicity properties, medicinal chemistry strategies need to be in continuous evolution and need to become even more multidisciplinary. In this review, we present how structure-based, ligand-based, and fragment-based drug design (SBDD, LBDD, and FBDD, respectively) and their respective techniques were used for the design and optimization of successful cases of New Molecular Entities (NMEs) approved by the Food and Drug Administration (FDA).

Antifolates are a class of drugs used as antibacterial, antiparasitic, and anticancer agents. This review focuses on 2-substituted-mercapto-quinazolin-4(3H)-one analogues as dihydrofolatereductase (DHFR) inhibitors. Several research work have concluded a structural model for this class of 2-thio-quinazoline derivatives to get compounds with remarkable biological activity. The pattern and orientation of the p-system substitutions with regard to the quinazoline nucleus manipulate the activity. The application of the obtained model criteria produced compounds 18, 20 and 21, which proved to be 4-8 times more active than the reference drug methotrexate (MTX, 1).

Quinoline, isoquinoline, and indoles are common heterocyclic compounds. They have many biological activities, such as antioxidant, anti-inflammatory, antibacterial, antitumor, anti-virus, anti-rheumatism, immunity regulation, expectorant, and analgesic. Over the past few centuries, traditional natural products have made great contributions to the discovery and development of new therapeutic agents. Many important drugs have been found from these three classes of compounds. In this mini-review, we mainly cover the research progress on antioxidant, anti-inflammatory, antibacterial, analgesic activities of quinoline, isoquinoline, and indole compounds over the past 20 years (2000- 2019). We aim to explore new characteristic groups or structures in the search for active lead compounds and provide a basis for rational drug design.

Depression is a mood disorder or affective disorder disease with depression as the main symptom. It has become a kind of mental disease that cannot be ignored in the world that seriously endangers human physical and mental health. Antidepressants commonly used in clinics generally have some defects, including slow action, unremarkable effects, and large side-effects. Therefore, there has a huge developing space for the research of new and effective therapeutic drugs to supplement or replace traditional drugs. The essential oil has obvious advantages in the treatment of depression and other emotional diseases, its aromatic odor can directly stimulate the olfactory nerves, and the lipophilic small- molecular compounds can cross the blood-brain barrier easily to play its regulatory role of releasing neurotransmitters and hormones related to depression, or adjusting the expression of brain-derived neurotrophic factor and proinflammatory cytokines. The pathogenesis of depression and the problems in traditional medication were illustrated, the research on the antidepressant effects and mechanism of essential oils in recent years is summarized, and the antidepressant chemical components in plant essential oils are reviewed in this article. The article provides scientific basis for an essential oil to be a new choice for relieving depression and treating depression.

SET protein is a multi-functional oncoprotein that is ubiquitously expressed in most tumor cells. Dysregulation of SET has been associated with many types of cancer. Due to ever-accumulating evidence of its strong correlation with both poor prognosis and drug resistance, the targeting of SET is starting to be explored. SET is currently regarded as a potential target for cancer therapy, and several inhibitors are being developed for clinical trials. In this review, the physiological and pathological functions of SET, as well as its antagonists, will be discussed along with the prospects and challenges involved with translating SET inhibitors into bona fide therapeutic options.

Aim: Terpenes are natural compounds found in several organisms belonging to the animal and plant kingdom, therefore, constitute the largest class of natural products and were a rich reservoir of candidate compounds for drug discovery. The review aims to focus on the extensive potential of the anti-cancer terpenoid components obtained from natural plant species which may lead to the development of a variety of derived terpenoids moieties. Method: Literature survey has been carried out to determine the potential of terpenoids. Result: The present article provides an overview of the development of the isoprene unit and the generation of the various types of terpenes that exhibits pharmacological potential. The anti-cancer activity of terpenoids appears promising and will potentially open more opportunities for cancer therapy. However, current studies are restricted to descriptive findings and some of them lack mechanistic insights and systematic structure--activity relationship studies. Future efforts into the systematic identification of the targets of terpenoids are believed to increase the chances of gaining breakthrough insights in the field. Conclusion: There is still hope that new therapeutic options for the control of cancer and any other painful syndromes will be developed from terpenes, which were proved to be great candidates for cancer therapeutics.

Fungi are recognized as key pathogens in immunocompromised patients. The invasive infection always remains a problem for clinicians due to high morbidity and mortality. The treatments of fungal infections are hampered by conventional drugs, which are associated with resistance. Drug resistance has become an important problem in a variety of infectious diseases. The rise in the incidence of fungal infections and drug resistance has intensified the need for alternative therapies that affect a new target. This new target must be a growth essential gene product like the stress pathway. It has been found that stress pathways can be a potential target in opportunistic fungal infection, which played an important role in the virulence of pathogens. It was helpful in protection from host defense, normal fungal growth, and antifungal drug resistance. The disruption of the pathway using alternative strategies (chemosensitization and photo-dynamics therapy) can be a novel approach in fighting fungal infections and for drug design.

Cancer treatment has become a major challenge amidst the resistance and relapse caused by the various treatments available. The PROteolysis TAargeting Chimera (PROTAC) technology involves the degradation of target protein against the inhibition by small drug molecules. The PROTACs with high potency and activity have been frequently reported; however, no PROTAC acting against cancer has reached the clinical trials. The concept of PROTACs involves the reduction in the disease-causing protein by its degradation through the ubiquitin-proteasomal enzyme system. This concept has attracted a lot of attention from both industry and academia due to its potential in drug discovery (in the form of PROTACs), which can conquer the resistance associated with current treatments of cancer. Thus, it is the need of the hour to identify and synthesize more PROTACs for a viable treatment of cancer. This article reviews the design, activity and effects produced in cancer by some recently developed PROTACs.

Background: Alzheimer’s disease (AD) is a multifactorial neurodegenerative disease, and a drug which targets a single protein would not provide a cure for this disease. Currently available drugs for AD are all palliative rather than curative. FDA approved only five drugs for the treatment of AD, which include tacrine, donepezil, galantamine, rivastigmine, and memantine. Tacrine has been discontinued due to its hepatotoxicity. The lack of therapeutic effectiveness of the single-target drugs and multifactorial etiology of AD have led to the design of multitarget directed ligands for AD. Objective: The researchers in this field are constantly making efforts to develop a drug which may prove to be the exact cure for this disease by exploring the different biological targets associated with AD. The present review comprises various multitarget approaches and tools used for finding out a lead compound or a new drug, which will provide a cure for AD. Methods: We have scrutinized and reviewed 75 research articles published in various peer reviewed journals in the last two decades in the field of multi target directed ligand approaches for the discovery of a new therapeutic agent for AD. Results: The review highlights the recent advances in the field of AD research and shows that the battle for the discovery of an effective drug for AD is in process and AD still remains an incurable disease for which treatment is just palliative. Conclusion: The review might be helpful for researchers working on multi target directed ligands against AD.

The central dogma of molecular biology explains the flow of genetic information from DNA to functional products such as proteins. In most cases, a linear relationship with a high correlation coefficient exists between the concentration of mRNA, the middle man, and the functional product. Untranslated regions (UTRs) of RNA form a considerable base pairing that contributes to the secondary and tertiary structures of mRNA. The interaction between the mRNA secondary structures (cis-elements), RNA-binding proteins (RBP) and miRs (trans-element) are critical determinants of mRNAs' fate and stability. Among different viral families, the positive sense (+) RNA viruses use the simplest possible strategy of replication and expression, as the same molecule functions both as a genome and mRNA. Additionally, nucleotide composition and codon usage of +RNA viruses are the closest to human codon adaptation index (CAI). Since the origin of replication of viral intermediate RNA molecules is at the 3'-end of the genome, the 3'UTR plays a role in viral RNA replication. Moreover, the messenger role of RNA likely places functional demands on the 3'UTR to serve a role typical of cellular mRNA. This article reviews the effect of 3'UTR of RNA viruses with positive sense and genomes on mRNA stability and translation improvement. A range of animal (e.g., Dengue, Sindbis, Corona and Polio) and plant (Barley yellow dwarf, Brome mosaic, Turnip crinkle, Tobacco mosaic, Cowpea mosaic and Alfalfa mosaic) viruses are examined to highlight the role of 3'UTR in viral survival and as a potential target for pharmaceutical applications.

Background: Brassica oleracea var. capitata f. alba (white cabbage) is a cruciferous vegetable used as a vegetable and traditional medicine all over the world. Different preparation from several parts of the plant- roots, shoots, leaves, and the whole plant are used to treat a wide range of diseases, including diabetes, cancer, gastric, inflammation, hypertension, hypercholesterolemia, bacterial, oxidation, and obesity. Objective: The aim of the current review is to evaluate the botany, distribution, traditional uses, phytochemistry, and pharmacological activities of B. oleracea var. capitata. Moreover, this review will guide to fill the existing gaps in information and highlight additional research prospects in the field of phytochemistry and pharmacology. Method: Various resources, including research papers, review papers, books, and reports, were collected to obtain overall information on Brassica oleracea var. capitata, which were obtained by an online search of worldwide-accepted scientific databases. Phytochemical constituents’ structures were drawn by ChemDraw software. Results: About 72 isolated phytochemical compounds of B. oleracea var. capitata have been collected from different articles, which included different types of compounds such as alkaloids, flavonoids, organic acids, glucosinolates, steroids, hydrocarbons, etc. Crude extracts and phytoconstituents of B. oleracea var. capitata have various pharmacological effects, including antidiabetic, anticancer, antihypertensive, anticholesterolemic, antioxidant, anti-inflammatory, antibacterial, anti-obesity, anticoagulant, and hepatoprotective. We have enlisted all these pharmacological data along with all the phytochemical constituents of Brassica oleracea var. capitata. Conclusion: The study was focused on the traditional uses, pharmacological activities, and phytochemistry of Brassica oleracea var. capitata, and the findings indicated that B. oleracea var. capitata is an important medicinal plant that shows several pharmacological effects. We hope our review of this plant will provide more basic and useful information and fill some research gaps for further investigation and drug design. Although we found some important traditional uses and pharmacological activities of Brassica oleracea var. capitata, there is insufficient work in the field of phytochemical activities.