Mini Reviews in Medicinal Chemistry - Volume 21, Issue 13, 2021

Background and Objective: Today, a new β-coronavirus called SARS-CoV-2 has emerged and it is causing a global pandemic. Inter-human transmission studies have indicated a significant role of aerosols in the transmission of many respiratory viruses. Hence, it is very important to decrease the spread of the virus through disinfectant agents. This review aimed to provide an overview related to possible alternative inhibitory molecules against this virus. Method: The literature search was performed in the MEDLINE electronic database using the public access known as NCBI-PUBMED. Keywords "coronavirus" and “SARS-CoV-2” and “COVID19” were used. No specific time range was used. Results: We provide a review related to structure, anti-coronavirus activity and molecular mechanism of natural substances and semisynthetic derivatives such as glycopeptides, lipopeptides, probiotics, surfactants, terpenes and resveratrol. We also include the latest in vitro experiments with anti-SARSCoV- 2 activity. We also provide the theoretical basis for discussing the prospects of such natural molecules as possible alternative anti-Coronavirus products, so as to develop a complete screening for future applications. Conclusion: In summary, this review suggest to investigate deeper several molecules most of which belong to natural substances to fight COVID19 disease.

A member of cathepsin enzymes called Cathepsin B is a cysteine-protease enzyme that plays significant role in metalloproteinase regulation. Cathepsin B stands out amidst other members of cathepsin because of its role in both normal body physiology and pathophysiology. Being an antiapoptotic and a pro-apoptotic agent, Cathepsin B has been reported to have deleterious effects, especially when its expression, activities, and distribution are outrageous. The over-expression of cathepsin B is traceable to dysregulation of one or more regulated steps involved in its synthesis. Consequently, the over-expression of cathepsin B contributes to the pathogenesis of different types of cancers - a global menace. Interestingly, the synthesis of this enzyme has been reported to be inhibited by several metal compounds, thus, curbing its involvement in carcinogenesis. In this review, the synthesis, structure, localization, and roles of cathepsin B in carcinogenesis were explored. Likewise, we also discussed the capacity of metallic compounds to inhibit this enzyme. Metals such as gold, ruthenium, palladium, Iridium, and Tellurium demonstrated remarkable activity toward cathepsin B of different modes. A relationship between cytotoxicity and inhibition constants was observed.

Bioactive compounds found in food and medicinal plants contribute to maintaining health and treating illnesses. For example, hydroxycinnamic acids, such as ferulic acid, are widely present in nature and have several pharmacological properties, including antioxidant, anti-inflammatory, and beneficial effects in parameters of diabetes and hyperlipidemia. The results of studies in animal models and in vitro experiments of ferulic acid suggest its high therapeutic and preventive potential against several pathological disorders, such as cardiovascular diseases. Therefore, in this review, the bioactivities of ferulic acid on the cardiovascular system are described, including the discussion of the mechanisms of action in the various components of the system. In this review, we discuss the pharmacological properties of this versatile natural product in aspects of cardiovascular health, including cardioprotective and antihypertensive actions, and on the metabolism of lipids, diabetes, and thrombosis.

Pluripotent stem cells of the bone marrow are stimulated by different cytokines to proliferation and differentiation into various types of blood cells. These cytokines are mostly glycoproteins. Erythropoietin stimulates stem cells to the formation of erythrocytes while colony-stimulating factors cause the formation of different types of white blood cells. Stem cell factors play an important role in the maintenance and survival of blood cells of all types. Thrombopoietin stimulates stem cells to proliferation and formation of blood platelets. Granulocyte colony-stimulating factor is probably the most important drug in use. It stimulates stem cells to the formation of neutrophile granulocytes. It is often used in recombinant forms such as filgrastim in the treatment of neutropenia in cancer chemotherapy or AIDS. Its pegylated conjugates such as pegfilgrastim are also available. Its activity can be supported by plerixafor, a small molecule – bicyclam derivative acting as an indirect agonist of stem cells factor. It acts as an antagonist of CXCR4 receptor activation of which brakes hematopoiesis. The treatment of conditions accompanied by thrombocytopenia such as idiopathic thrombocytopenic purpura is currently not performed by thrombopoietin but synthetic agonists of its receptor are preferred. Romiplostim is a peptibody. It consists of a protein part interacting with the thrombopoietin receptor which is, however, different from thrombopoietin, and of Fc fragment of immunoglobulin G1. In contrast, small molecule thrombopoietin receptor agonists represented by eltrombopag can be given orally unlike all of the above.

During cancer progression, the unrestricted proliferation of cells is supported by the impaired cell death response provoked by certain oncogenes. Both autophagy and apoptosis are the signaling pathways of cell death, which are targeted for cancer treatment. Defects in apoptosis result in reduced cell death and ultimately tumor progression. The tumor cells lacking apoptosis phenomena are killed by ROS- mediated autophagy. The autophagic programmed cell death requires apoptosis protein for inhibiting tumor growth; thus, the interconnection between these two pathways determines the fate of a cell. The cross-regulation of autophagy and apoptosis is an important aspect to modulate autophagy, apoptosis and to sensibilise apoptosis-resistant tumor cells under metabolic stress and might be a rational approach for drug designing strategy for the treatment of cancer. Numerous proteins involved in autophagy have been investigated as the druggable target for anticancer therapy. Several compounds of natural origin have been reported, to control autophagy activity through the PI3K/Akt/mTOR key pathway. Diosgenin, a steroidal sapogenin has emerged as a potential candidate for cancer treatment. It induces ROS-mediated autophagy, inhibits PI3K/Akt/mTOR pathway, and produces cytotoxicity selectively in cancer cells. This review aims to focus on optimal strategies using diosgenin to induce apoptosis by modulating the pathways involved in autophagy regulation and its potential implication in the treatment of various cancer. The discussion has been extended to the medicinal chemistry of semi-synthetic derivatives of diosgenin exhibiting anticancer activity.

Coronavirus spreads from one to another person, either by touching the hands or by touching the surface contaminated with this virus, and then touching the nose or mouth. COVID-19 infected human symptoms are like pneumonia symptoms, dry cough and high fever. Upper respiratory tract infections symptoms and sore throat are rare. It was first notified in China dated 12th December 2019 as a respiratory illness. In addition to travel restrictions and quarantine measures, everyone should follow the World Health Organization's advice guidelines on the management of humans infected with known or suspected infection with the SARS-CoV-2 virus at the personal level. The development of vaccine or medicines for the same is in progress and this short review will summarize the most potential candidates such as Remdesivir, Lopinavir and Ritonavir, Chloroquine, Hydroxychloroquine, Hydroxychloroquine with Azithromycin, Favipiravir, Umifenovir, and Ribavirin for its medicinal treatment.

The death toll associated with cancer worldwide is constantly on the increase. Efforts to combat and treat the different forms of this disease is also evolving. Nasopharyngeal carcinoma (NPC) is a lethal form of cancer, which is prevalent in Southern China, that is normally treated by using radiotherapy. Here, we will review products obtained from natural sources that have potential cytotoxic and apoptotic properties against NPC. These include grifolin, dihydroartemisinin, luteolin, honokiol, indole-3-carbinol, caffeic acid phenethyl ester, 6-O-angeloylenolin, cucurbitacin E, genistein, helenalin, celastrol, coronarin D, quercetin, trans-cinnamaldehyde, 5'-epimer episilvestrol, silvestrol, arnicolide D, brevilin A, and baicalin hydrate. Ethyl acetate extracts of Wedelia chinensis and aqueous extracts of Ajuga bracteosa are also included although the bioactive compounds involved have yet to be identified. The known mechanism of action of these products is discussed. It is anticipated that one or more of these substances may provide the general population with alternative and cost-effective ways to combat this fatal disease.

The Mediterranean diet (MD) is becoming a milestone for the prevention of chronic diseases, such as cardiovascular diseases (CVDs), Alzheimer’s and Parkinson’s disease. Ancel Keys in the 1950’s showed a low mortality rate, particularly for coronary heart disease, among people resident in the Mediterranean area. The MD is characterized by the intake of the high amount of vegetables, fruit, and cereals and regular but moderate consumption of wine, fish, and dairy products, while olive oil is the main source of culinary fat. Therefore, it is principally a plant-based diet rich in polyphenols, a heterogeneous category of compounds with different properties and bioavailabilities. Among polyphenols, anthocyanins have been combined into the human food regime for centuries. They have been utilized as traditional herbal remedies for their ability to treat several conditions, as potent anti-oxidants, anti-diabetic and anti-carcinogenic compounds. This review summarizes our knowledge on the health-enhancing component of the anthocyanins-rich diet.

The complexity of Chagas disease is still a challenge in endemic regions and an emergent public health problem in non-endemic countries. The causative agent of this neglected tropical disease, Trypanosoma cruzi, is mainly transmitted by triatomine vectors and possesses multiple epidemiologically important strains. Current chemotherapeutics are outdated and their limited efficacy is one of the major reasons for treatment discontinuation. In this context, the development of novel, safe and economically accessible antichagasic drugs is required. Various classes of heterocycles and natural compounds have been described as potential antichagasic scaffolds, and coumarins are no exception. These versatile compounds have a wide spectrum of biological activities, and numerous natural and synthetic coumarins have been reported with antichagasic potential. This review aims to discuss the available literature between 2001 and 2020 regarding natural and synthetic coumarins with anti- Trypanosoma cruzi activity. Moreover, some of the studies herein comprised are dedicated to the potential of coumarins to inhibit promising targets in Trypanosoma cruzi.

Background: Metal-organic frameworks (MOFs) possess adjustable aperture, high load capacities, tailorable structures, and excellent biocompatibilities for their use as drug delivery carries in cancer therapy. Until now, Zr-MOFs, in particular, combine optimal stability towards hydrolysis and post synthetic modification with low toxicity, and are widely studied for their excellentbiological performance. Introduction: This review comprises the exploration of Zr-MOFs as drug delivery devices (DDSs) with a focus on various new methods, including chemotherapy (CT), photodynamic therapy (PDT), photothermal therapy (PTT), sonodynamic therapy (SDT), radiotherapy, immunotherapy, gene therapy and related combined therapies, which all generate reactive oxygen species (ROS) to achieve high efficiency of tumor therapy. Conclusion: We described and summarized these pertinent examples of the therapeutic mechanisms and highlighted the antitumor effects of their biological application both in vitro and in vivo. The perspectives on their future applications and the analogous challenge of the Zr-MOFs materials are given.

Phytochemicals play a vital role as drugs for the treatment of various autoimmune, viral, and cancerous diseases. Rotenoids, a type of isoflavone compounds present in plants genus Boerhaavia sp., Mirabilis sp. and Abronia sp. which belong to the Nyctaginaceae family, are traditionally used as pesticides and insecticides. Boeravinones are groups of rotenoid compounds widely used as drugs or drug adjuvants for the treatment of various diseases. Extraction of rotenoids in various solvents, purification of rotenoids in various chromatographic technique studies, and the characterization of functional groups of rotenoids in various spectroscopic techniques have been reported. Biological applications of rotenoids such as anti-cancerous, antioxidant, anti-inflammatory, antimicrobial, and cytotoxic activities have been discussed. This review summarizes the extraction, isolation, purification, and characterization of rotenoid compounds and their effect on the treatment of cancer, inflammatory, spasmolytic, autoimmune, and microbial diseases.

Background: Coronavirus disease 2019 (COVID-19) outbreak was declared as an emerging global public health concern on 30th January 2020. This novel coronavirus (SARS-CoV-2) outbreak was first identified in Wuhan city, China, which soon affected around 185 countries and territories all over the world through various transmission mechanisms. To date, no permanent cure has been found, due to which this pandemic threatens humanity for its very existence. Objective: In light of the rising menace, this review aims at providing collective and prominent information on the current outbreak, covering its origin, structure, transmission, clinical features, potential treatment approaches, and clinical trial details. Methods: The literature published in Scopus and PubMed indexed journals were reviewed, and clinical trial data was retrieved from the ClinicalTrials.gov database. Results: Present review puts forth detailed insights on history, epidemiology, structure, genetic makeup, reservoirs, entry mechanisms, reproduction capacity, pathogenesis, routes of transmission, clinical features, diagnostics, the role of chloroquine in treatment, current promising therapies, and vaccination trials. Conclusion: At present, early detection, isolation of infected patients, and supportive care with a few recently USFDA approved alternative medications are being used as per the standard government guidelines. Due to insufficient availability of proof regarding current therapies to produce therapeutic activity against COVID-19, safety precautions, prevention methods, hygiene maintenance and management therapy with intensive care medicine is the only way to fight this current situation.

A sizeable proportion of currently marketed drugs come from heterocycles. The heterocyclic moiety 5-pyrazolone is well known five-membered ring containing nitrogen. Derivatives of this wonder nucleus have exhibited activities as diverse as antimicrobial, anti-inflammatory, analgesic, antidepressant, anticonvulsant, antidiabetic, antihyperlipidemic, antiviral, antitubercular, antioxidant, anticancer and antiviral, including action against severe acute respiratory syndrome (SARS) or 3C protease inhibitor. A number of drugs based on this motif have already made it to the market. Standard texts and literature on medicinal chemistry cite different approaches for the synthesis of 5- pyrazolones. The present review provides an insight view to 5-pyrazolone synthesis, their biological profile and structure-activity relationship studies.

The article “Potential health benefits of broccoli- a chemico-biological overview, published in Mini-Rev Med Chem 2009 Jun;9(6):749-59. By Hannah R. Vasanthi, Subhendu Mukherjee and Dipak K. Das” has been retracted by the Editorial office of the journal Mini-reviews in Medicinal Chemistry, as the text in this review article are from sources which have been retracted or under investigation on the basis of data fabrication and falsification, authorship misconduct, duplicate publication, unethical research practices, text recycling/self-plagiarism, and unresolved concerns about data integrity and research conduct. The authors were informed of this complaint and were requested to give justification on the matter in their defense [1]. Some sources that have been retracted are as follows: 1) Agarwal et al. Dynamic Action of Carotenoids in Cardioprotection and Maintenance of Cardiac Health, Molecules 2012, 17, 4755-4769. http: https://pubmed.ncbi.nlm.nih.gov/24896014/ 2) Nagendran Balasundram, KalyanaSundram, SamirSamman. Phenolic compounds in plants and agri-industrial byproducts: Antioxidant activity, occurrence, and potential uses. Food Chemistry 2006, 99(1), 191-203. https://www.sciencedirect.com/science/article/abs/pii/S0308814605006242 Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused. The Bentham Editorial Policy on Article Retraction can be found at https://benthamscience.com/editorial-policies-main.php. REFERENCES [1] Hannah R Vasanthi, Subhendu Mukherjee, Dipak K Das. Potential health benefits of broccoli- a chemico-biological overview. Mini Rev Med Chem., 2009, 9(6), 749-759. doi: 10.2174/138955709788452685. https://pubmed.ncbi.nlm.nih.gov/19519500/ Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.