Mini Reviews in Medicinal Chemistry - Volume 21, Issue 12, 2021

Among many reactive oxygen species (ROS), which are constantly generated during oxidative stress in cellular membranes, the formation and subsequent reactivity of ubiquitous 4-hydroxy-2- nonenal (HNE) with nearby amino acids and lipids represent one of the main research targets in cell physiology in the last decades. Starting from the first synthesis of HNE in 1967, the chemistry and reactivity of HNE are constantly under intense scrutiny. This review shows recent advances in the field, which are discussed with the special emphasis on revealing intricate details of numerous reaction mechanisms of HNE with lipids and amino acids, with the goal of understanding the reactivity of HNE at the molecular level.

Propolis is a natural product made from the mixture of plant resin, saliva and wax collected by bees. It has been studied and concerned because of its high medicinal value and broad application prospects. Propolis has complex components, which can act on the body through multi-pathways and multi-targets to play the role of antibacterial, anti-inflammatory, anti-tumor and so on, and it can be used as an important resource for the prevention and treatment of oral diseases. In this review, we mainly reviewed components of propolis and its physiological activities against oral diseases, as well as the new dosage forms and applications of propolis in oral treatment. The purpose of this review is to explore the advantages of propolis in the treatment of oral diseases and the wide application of propolis in the field of oral health.

Background: Currently, the pharmacological management of Alzheimer's disease is based on several chemical structures, represented by acetylcholinesterase and N-methyl-D-aspartate (NMDA) receptor ligands, with still unclear molecular mechanisms and severe side effects. For this reason, a challenge for Alzheimer's disease treatment remains to identify new drugs with reduced side effects. Recently, the natural compounds, particularly, certain chemical compounds identified in the essential oil of peppermint, sage, grapes, sea buckthorn, have increased interest as possible therapeutics. Objectives: In this paper, we have summarized data from the recent literature on several chemical compounds extracted from Salvia officinalis L., with therapeutic potential in Alzheimer's disease. Methods: In addition to the wide range of experimental methods performed in vivo and in vitro, we also presented some in silico studies of medicinal compounds. Results: Through this mini-review, we presented the latest information regarding the therapeutic characteristics of natural compounds isolated from Salvia officinalis L. in Alzheimer's disease. Conclusion: Thus, based on the information presented, we can say that phytotherapy is a reliable therapeutic method in a neurodegenerative disease.

Recently, a sudden outbreak of novel coronavirus disease (COVID-19) was caused by a zoonotic virus known as severe acute respiratory syndrome coronavirus (SARS-CoV-2). It has caused pandemic situations around the globe affecting the lives of millions of people. So far, no drug has been approved for the treatment of SARS-CoV-2 infected patients. As of now, more than 1000 clinical trials are going on for repurposing of FDA-approved drugs and for evaluating the safety and efficiency of experimental antiviral molecules to combat COVID-19. Since the development of new drugs may require months to years to reach the market, this review focusses on the potential of existing small molecule FDA approved drugs and the molecules already in the clinical pipeline against viral infections like HIV, hepatitis B, Ebola virus, and other viruses of coronavirus family (SARS-CoV and MERS-CoV). The review also discusses the natural products and traditional medicines in clinical studies against COVID-19. Currently, 1978 studies are active, 143 completed and 4 posted results (as of June 13, 2020) on clinicaltrials.gov.

The transcriptional factor PPAR-γ belongs to the nuclear receptor family, which has become a potential therapeutic target for several neurodegenerative diseases and metabolic disorders. Interestingly, PPAR-γ has been reported to have beneficial effects in various chronic neurological conditions via upregulation of its transcriptional co-activator PGC-1α and followed by regulation of multiple molecular events. Although several factors contribute to the progression of neurodegeneration, the dysfunction of PGC-1α expression is primarily interlinked with the pathogenesis of major neurodegenerative diseases. This review gives an insight that ligand-dependent activation of PPAR-γ by glitazones could initiate the structural conformational changes of the secondary proteins, thus recruiting the PGC-1α to form a stable regulatory complex that hampers the various molecular pathways contributing to neurodegeneration. The promising outcomes of the preliminary in silico studies included in this review support that PPAR-γ dependent activation of central PGC-1α signaling by novel glitazones is an encouraging strategy to enhance the oxy-radicals detoxifying system, antiinflammatory responses, and mitochondrial biogenesis required for neuroprotection in various neurodegenerative conditions.

Background: Multidrug resistance (MDR) is the resistance of cancer cells against a variety of currently used antineoplastic agents with diverse structural scaffolds and different anticancer mechanisms. It has been recognized as one of the major impediments to the successful treatment of cancer, leading to the metastasis and relapse of malignant diseases. Introduction: Collateral sensitivity (CS) is the characteristic of certain chemicals to kill the drugresistant sublines selectively over the parental cell lines from which the resistant cells were generated. The research and development of new drug candidates with collateral sensitivity will be an efficient approach to conquer multidrug resistance in cancer. We aim to provide an update on the discovery of natural products with collateral sensitivity. Results and Conclusion: The review focused on the characterized anticancer natural products and their derivatives with collateral sensitivity, their working mechanisms, and related structure-activity relationships, emphasizing recently identified CS compounds. According to their structural features, these MDR-targeting compounds were mainly classified into the following categories: flavonoids, terpenoids, stilbenes, alkaloids and quinones. The exploration of molecular mechanisms of collateral sensitivity and structural features of anticancer agents with collateral sensitivity provided an effective approach for the clinic treatment of MDR in cancer.

Introduction: Malaria, a devastating infectious parasitic disease, has been recognized by the World Health Organization (WHO) as a major public health problem worldwide. It is one of the leading causes of morbidity and mortality in developing countries. There are a number of antimalarial drugs available in the market to combat this deadly disease. The situation is further worsened due to the emergence of resistant strains of Plasmodium falciparum, which warrants the search for novel antimalarial drugs capable of acting at multiple targets to expand the current antimalarial drug arsenal for better therapeutic outcome. Objectives: This review aimed to provide the reader with the recent advances and progress made in the development of chemotherapeutic agents for malaria. Methods: Literature review data on the chemistry and antimalarial activity of natural and synthetic heterocyclic compounds published in the last ten years were compiled by referring to various peerreviewed journal websites and medical search engines. Results and Discussion: This review covers the recent advances and progress made in the treatment strategies, patent granted, synthetic approaches, mechanism of action with more emphasis on a Structure- activity Relationship (SAR) of potential chemotherapeutic agents as antimalarial agents which could pave the way for the development of more effective and potent antimalarial agents. This review might interest fellow researchers working on the development of novel antimalarial drug candidates with better therapeutic index. Conclusion: Based on the literature covered in the current review article and seeing the recent trends, authors are of the opinion that the multi-target conjugated hybrid approach is the best strategy to discover and develop effective antimalarial agents.

Triterpenes are a wide and important group of compounds that have several promising pharmacological properties, such as hepatoprotective, anti-inflammatory, anti-HIV, antioxidant, or anticancer activities. Such potent substances can be successfully incorporated in more complex chemical systems e.g. codrugs or pro-drugs that have a better pharmacological profile. The codrug is connected with a drug formation pathway to chemically cohere at least two drug molecules to improve positive therapeutic efficiency or decrease side effects. The codrug can be cleaved in the organism to generate effective compounds previously used as substrates. This article presents an overview of codrugs that consist of pentacyclic triterpene moiety that is chosen as a basic codrug moiety due to their wide range of vital activities and another drug molecule fragment. It was found that triterpenoid codrugs are characterized by a wide range of biological activities. However, most of them have anticancer potency.

Memory remains an obligatory regime of the human brain, and impaired memory causes serious obstacles in our everyday life. Alzheimer’s disease (AD) is one such neurodegenerative disease which mostly affects the elderly population, above the age of 60; marked by cognitive impairment of memory. Besides the known targets of AD against the several etiologies known to date, the zone of epigenetics has recently evolved as an ingenious field in AD. Epigenetic modifications do not affect DNA sequence but only long-term gene expression. Considering the complex multifactorial nature of AD, we herein discuss the various epigenetic targets which might give rise to potential therapeutic approaches. We reviewed the possible epigenetic targets for AD-like HDAC, Sirtuins, glial cells, miRNA and epigenetic modifications like DNA methylation. A deeper insight into these target areas can surely evolve AD diagnosis and therapeutics.

Since 1887, phenoxazine derivatives have attracted the attention of chemists due to their versatile utility, industrially and pharmacologically. Literature is found abundant with various pharmacological activities of phenoxazine derivatives like antitumor, anticancer, antifungal, antibacterial, anti-inflammatory, anti-diabetic, anti-viral, anti-malarial, anti-depressant, analgesic and many other drug resistance reversal activities. This review covers a detailed overview of the pharmacological application of phenoxazine nucleus, its chemistry and reactivity, and also illustrating the incorporation of different groups at different positions enhancing its biological application, besides some synthetic procedures.

Andrographis paniculata (Burm.f.) Nees (Acanthaceae) is a herbaceous plant and is commonly called 'King of Bitters'. It has gained attraction as a potential hepatoprotective agent and a natural molecule with various biological activities viz. anticancer, immunomodulatory, anti-inflammatory, antibacterial, neuroprotective, and so on. The andrographolide is one of the main diterpenoids responsible for the drug's bitter taste and various therapeutic activities. The poor cellular permeability, solubility and short biological half-life of its pure components limit its distribution to the target tissue. To conquer this obstacle, various researchers worldwide have been working on designing the synthetic derivatives of its active components and nanoformulations to improve the drug's efficiency and selectivity to develop more active leads for biomedical applications. This article discussed the recent research on synthetic derivatives, including their possible therapeutic applications and structure-activity relationship (SAR). Additionally, this article also presents essential information concerning the various nanoformulations developed to increase the delivery of pure compound/plant extract to the target site, thereby improving the drug's efficacy for multiple ailments.

The compound 4-hydroxy-3-methoxycinnamic acid, named ferulic acid (FA), is a ubiquitous phenolic compound distributed extensively in the plant kingdom. Ferulic acid is a boon. It has immense potential therapeutic effects in treating diabetes, cancer, pulmonary and CVS diseases majorly due to its antioxidant and anti-inflammatory action. Ferulic acid exhibits a wide variety of biological activities such as, anticarcinogenic, antiallergic, antimicrobial, antiviral, hepatoprotective, metal chelation, activation of transcriptional factors, modulation of enzyme activity, gene expression as well as signal transduction. This active ingredient's structural characteristics make it an optimal substrate to form or synthesise various derivatives and its formulations. The present review addresses structure of ferulic acid, its pharmacodynamic parameters, applications, and its various derivatives. Besides, the review also aims to cover the main aspects related to the use of ferulic acid in the food and health industry and lists various published patents on Ferulic acid.