Mini Reviews in Medicinal Chemistry - Volume 22, Issue 13, 2022

Given the lack of success in the development of effective drugs to treat COVID-19, which show “game-changing” potential, it is necessary to explore drugs with different modes of action. Single mode-of-action drugs have not been succeeded in curing COVID-19, which is a highly complex disease. This is the case for direct antivirals and anti-inflammatory drugs, both of which treat different phases of the disease. Aptamers are molecules that deliver different modes of action, allowing their effects to be bundled, which, when combined, support their therapeutic efficacy. In this minireview, we summarise the current activities in the development of aptamers for the treatment of COVID-19 and long-COVID. A special emphasis is placed on the capability of their multiple modes of action, which is a promising approach for treating complex diseases such as COVID-19.

Matrine, a tetracyclo-quinolizidine alkaloid, is isolated from the industrial crop plant Sophora flavescens. Due to a wide range of pharmacological and agricultural properties, the research on the phytochemistry, pharmacology, toxicology, and mechanisms of action of matrine and its derivatives has received much attention. On the other hand, to improve their biological activities, the study on structural optimizations and structure-activity relationships of matrine and its derivatives has also attached more and more importance. In this review article, the updates regarding the advances in bioactivities, mechanisms of action, structural modifications, and structure-activity relationships of matrine and its derivatives from 2017 to 2020 are presented. We hope that this review will provide a reference for the development and application of matrine and its derivatives as drugs or pesticides in the future.

Every day, new cases of cancer patients whose recovery is delayed by multidrug resistance and chemotherapy side effects are identified, which severely limit treatment options. One of the most recent advances in nanotechnology is the effective usage of nanotechnology as drug carriers for cancer therapy. As a consequence, heterocyclic nanocarriers were put into practice to see whether they could have a better cure with positive results. The potential of a therapeutic agent to meet its desired goal is vital to its success in treating any disease. Heterocyclic moieties are molecules that have a wide variety of chemically therapeutic functions as well as a significant biological activity profile. Heterocyclic nanoformulations play an important role in cell physiology and as possible arbitrators for typical biological reactions, making them valuable in cancer research. As a result, experts are working with heterocyclic nanoformulation to discover alternative approaches to treat cancer. Due to their unique physicochemical properties, heterocyclic compounds are real cornerstones in medicinal chemistry and promising compounds for the future drug delivery system. This review briefly explores the therapeutic relevance of heterocyclic compounds in cancer treatment, various nanoformulation, and actively describes heterocyclic magnetic nano catalysts and heterocyclic moiety, as well as their mode of action, which have favorable anti-cancer effects.

Diphyllin glycosides (DG) are a type of arylnaphthalene lignans isolated from different plants, and their synthetic derivatives have shown effective antiviral, cytotoxic, hypotensive and diuretic effects at very low concentrations similar to standard drugs that are under clinical use. The biological activities of the DG interfere with signaling pathways of viral infection and cancer induction. The sugar moieties of DG enhance bioavailability and pharmacological activities. The promising results of DG at nanomolar concentrations under in vitro and in vivo conditions should be explored further with clinical trials to determine its toxic effects, pharmacokinetics and pharmacodynamics. This may help identify suitable antiviral and anticancer drugs in the near future. Considering all these activities, the present review is focused on the chemical aspects of DG with a detailed account of the mechanisms of action of DG. An attempt is also made to comment on the status of clinical trials involving DG along with the possible limitations in studies based on available literature till September 2020.

Bridged peptide macrobicycles (BPMs) from natural resources belong to types of compounds that are not investigated fully in terms of their formation, pharmacological potential, and stereo- chemical properties. This division of biologically active congeners with multiple circular rings has merits over other varieties of peptide molecules. BPMs form one of the most hopeful grounds for the establishment of drugs because of their close resemblance and biocompatibility with proteins, and these bio-actives are debated as feasible, realistic tools in diverse biomedical applications. Despite huge potential, poor metabolic stability and cell permeability limit the therapeutic success of macrocyclic peptides. In this review, we have comprehensively explored major bicyclic peptides sourced from plants and mushrooms, including β^s-leucyl-tryptophano-histidine bridged and tryptophanocysteine bridged peptide macrobicycles. The unique structural features, structure-activity relationship, synthetic routes, bioproperties, and therapeutic potential of the natural BPMs are also discussed.

Lipid metabolism disorder is a multifactor issue, which contributes to several serious health consequences, such as obesity, hyperlipidemia, atherosclerosis diabetes, non-alcoholic fatty liver, etc. Tannins, applied as naturally derived plants, are commonly used in the study of lipid metabolism disease with excellent safety and effectiveness while producing less toxic and side effects. Meanwhile, recognition of the significance of dietary tannins in lipid metabolism disease prevention has increased. As suggested by existing evidence, dietary tannins can reduce lipid accumulation, block adipocyte differentiation, enhance antioxidant capacity, increase the content of short-chain fatty acids, and lower blood lipid levels, thus alleviating lipid metabolism disorder. This study is purposed to sum up and analyze plenty of documents on tannins, so as to provide the information required to assess the lipid metabolism of tannins.

Inhibition of cholinesterases is a common strategy for the treatment of several disorders, especially Alzheimer´s disease. In vitro assays represent a critical step towards identifying molecules with potential anticholinesterase effect. This study aimed at providing a comprehensive review of the methodologies used in vitro for the anticholinesterase activity based on the spectrophotometry of Ellman’s method. This work used two databases (PubMed and ScienceDirect) to search for original articles and selected publications between 1961 and 2019, which reported in vitro spectrophotometry assays for anticholinesterase activity. After the search process and the selection of publications, the final sample consisted of 146 articles published in several journals submitted by researchers from different countries. Although the studies analyzed in this work are all within the same conception of in vitro tests based on Ellman’s method, one can observe a wide divergence in the origin and concentration of enzyme, the choice and pH of the buffer, the concentration of the substrate, the sample diluent, incubation time, temperature, and time of the spectrophotometric reading interval. There is no consensus in the methodology of studies with in vitro tests for anticholinesterase assessment. The methodological variations related to kinetic parameters may interfere in the characterization of cholinesterase inhibitors.