Mini Reviews in Medicinal Chemistry - Volume 21, Issue 4, 2021

β-Carboline, a naturally occurring indole alkaloid, holds a momentous spot in the field of medicinal chemistry due to its myriad of pharmacological actions like anticancer, antiviral, antibacterial, antifungal, antileishmanial, antimalarial, neuropharmacological, anti-inflammatory and antithrombotic among others. β-Carbolines exhibit their pharmacological activity via diverse mechanisms. This review provides a recent update (2015-2020) on the anti-infective potential of natural and synthetic β-carboline analogs focusing on its antibacterial, antifungal, antiviral, antimalarial, antileishmanial and antitrypanosomal properties. In cases where enough details are available, a note on its mechanism of action is also added.

Background: The global incidence of type 2 diabetes mellitus (T2DM) has enthused the development of new antidiabetic targets with low toxicity and long-term stability. In this respect, free fatty acid receptor 1 (FFAR1), which is also recognized as a G protein-coupled receptor 40 (GPR40), is a novel target for the treatment of T2DM. FFAR1/GPR40 has a high level of expression in β-cells of the pancreas, and the requirement of glucose for stimulating insulin release results in immense stimulation to utilise this target in the medication of T2DM. Methods: The data used for this review is based on the search of several scienctific databases as well as various patent databases. The main search terms used were free fatty acid receptor 1, FFAR1, FFAR1 agonists, diabetes mellitus, G protein-coupled receptor 40 (GPR40), GPR40 agonists, GPR40 ligands, type 2 diabetes mellitus and T2DM. Results: The present review article gives a brief overview of FFAR1, its role in T2DM, recent developments in small molecule FFAR1 (GPR40) agonists reported till now, compounds of natural/plant origin, recent patents published in the last few years, mechanism of FFAR1 activation by the agonists, and clinical status of the FFAR1/GPR40 agonists. Conclusion: The agonists of FFAR1/GRP40 showed considerable potential for the therapeutic control of T2DM. Most of the small molecule FFAR1/GPR40 agonists developed were aryl alkanoic acid derivatives (such as phenylpropionic acids, phenylacetic acids, phenoxyacetic acids, and benzofuran acetic acid derivatives) and thiazolidinediones. Some natural/plant-derived compounds, including fatty acids, sesquiterpenes, phenolic compounds, anthocyanins, isoquinoline, and indole alkaloids, were also reported as potent FFAR1 agonists. The clinical investigations of the FFAR1 agonists demonstrated their probable role in the improvement of glucose control. Though, there are some problems still to be resolved in this field as some FFAR1 agonists terminated in the late phase of clinical studies due to “hepatotoxicity.” Currently, PBI-4050 is under clinical investigation by Prometic. Further investigation of pharmacophore scaffolds for FFAR1 full agonists as well as multitargeted modulators and corresponding clinical investigations will be anticipated, which can open up new directions in this area.

In the present study, authors want to encourage the research exertions through structureactivity relationship for the identification of effective molecules for the treatment of Human immunodeficiency virus because nowadays AIDS is considered as one of the main causes of death in human beings. A diversity of biological resources has been searched and developed for the treatment of HIV but unfortunately, until now, no medicine is found to be fully effective and safe for the cure of patients. Human immunodeficiency virus is a type of lentivirus which causes the infection of HIV and once it enters the human body, it stays for a longer period of time triggering immunodeficiency syndrome. For searching and developing new potent and effective anti-HIV molecules, medicinal chemists have engaged in countless targets with the structure-activity relationship (SAR) of molecules and on this basis, many antiretroviral therapies have been developed to cure HIV infection. Most of these new searched molecules have been found to be clinically active against various types of AIDS patient and auxiliary research in this area may lead to better treatment in the near future. This article encompasses and highlights the recent advancement of innumerable inhibitors laterally through synthetic, semi-synthetic and structure-activity relationship approaches.

Wound healing is a process that starts with the inflammatory response after the occurrence of any damage. This process initiates by restoring the wound surface coating tissue, migrating fibroblasts to form the required collagen, forming a healing tissue and finally, leading to contortion and extraction of the wound. Today, various drugs are used to heal wounds. However, the drugs used to repair wounds have some defects and side effects. In spite of all attempts to accelerate wound healing definitely, no safe drug has been introduced for this purpose. Therefore, the necessity to identify herbal plants in ethnopharmacology and ethnobotany documents with healing effects is essential. In this article, we tried to review and present effective Iranian medicinal plants and herbal compounds used for wound healing. Searching was performed on databases, including ISI Web of Science, PubMed, PubMed Central, Scopus, ISC, SID, Magiran and some other databases. The keywords used included wound healing, skin treatment, medicinal plants, ethnobotany, and phytotherapy. In this regard, 139 medicinal plants effective on wound healing were identified based on ethnopharmacology and ethnobotanical sources of Iran. Plants such as Salvia officinalis, Echium amoenum, Verbascum spp., G1ycyrrhiza glabra, Medicago sativa, Mentha pulegium, Datura stramonium L., Alhagi spp., Aloe vera, Hypericum perforatum, Pistacia atlantica and Prosopis cineraria are the most important and useful medicinal plants used for wound healing in Iran. These native Iranian medicinal plants are rich in antioxidants and biological compounds and might be used for wound healing and preparation of new drugs.

Neuroinflammation is a typical feature of many neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. Microglia, the resident immune cells of the brain, readily become activated in response to an infection or an injury. Uncontrolled and overactivated microglia can release pro-inflammatory and cytotoxic factors and are the major culprits in neuroinflammation. Hence, research on novel neuroinflammatory inhibitors is of paramount importance for the treatment of neurodegenerative diseases. Bacterial lipopolysaccharide, widely used in the studies of brain inflammation, initiates several major cellular activities that critically contribute to the pathogenesis of neuroinflammation. This review will highlight the progress on terpenoids, an important and structurally diverse group of natural compounds, as neuroinflammatory inhibitors in lipopolysaccharidestimulated BV-2 microglial cells over the last 20 years.