Mini Reviews in Medicinal Chemistry - Volume 22, Issue 14, 2022

In 2018, James Allison and Tasuku Honjo received the Nobel Prize in physiology or medicine to discover tumor therapy by inhibition of negative immune regulation. Immunotherapy stimulates T-cells to fight cancer cells by blocking different immune checkpoint pathways. The interaction between programmed cell death 1 (PD-1) and its ligand PD-L1 (Programmed cell death ligand 1) is one of the main pathways. Of note, interfering with this pathway is already exploited in clinical cancer therapy, demonstrating that it is one of the key factors involved in the immune escape mechanism of cancer. The development of monoclonal antibodies (mAbs) that possess the ability to inhibit the interactions between PD-1/PD-L1 has radically made the difference in cancer immunotherapy. Yet, due to the many drawbacks of this therapy, the research shifted its efforts towards the development of novel small molecules. This may constitute hope and an arduous challenge in fighting cancer. This paper reviews the recent primary literature concerning the development of novel small molecules able to block the interaction between PD-1 and its ligand PD-L1.

One of the common clinical complications of diabetes is diabetic neuropathy affecting the nervous system. Painful diabetic neuropathy is widespread and highly prevalent. At least 50% of diabetes patients eventually develop diabetic neuropathy. The four main types of diabetic neuropathy are peripheral neuropathy, autonomic neuropathy, proximal neuropathy (diabetic polyradiculopathy), and mononeuropathy (Focal neuropathy). Glucose control remains the common therapy for diabetic neuropathy due to limited knowledge on early biomarkers that are expressed during nerve damage, thereby limiting the cure through pharmacotherapy. Glucose control dramatically reduces the onset of neuropathy in type 1 diabetes but proves to be less effective in type 2 diabetes. Therefore, the focus is on various herbal remedies for prevention and treatment. There is numerous research on the use of anticonvulsants and antidepressants for the management of pain in diabetic neuropathy. Extensive research is being conducted on natural products, including the isolation of pure compounds like flavonoids from plants and their effect on diabetic neuropathy. This review focuses on the use of important flavonoids such as flavanols (e.g., quercetin, rutin, kaempferol, and isorhamnetin), flavanones (e.g., hesperidin, naringenin and class eriodictyol), and flavones (e.g., apigenin, luteolin, tangeretin, chrysin, and diosmin) for the prevention and treatment of diabetic neuropathy. The mechanisms of action of flavonoids against diabetic neuropathy by their antioxidant, anti-inflammation, anti-glycation properties, etc., are also covered in this review article.

Widely consumed worldwide, Nigella sativa (NS) is a medicinal herb commonly used in various alternative medicine systems, such as Unani and Tibb, Ayurveda, and Siddha. Recommended for regular use in Tibb-e-Nabwi (Prophetic Medicine), NS is considered one of the most notable forms of healing medicine in Islamic literature. Thymoquinone (TQ), the main component of the essential oil of NS, has been reported to have many properties, such as antioxidant, anti-inflammatory, antiviral, and antineoplastic. Its chemical structure indicates antiviral potential against many viruses, including the hepatitis C virus, human immunodeficiency virus, and other coronavirus diseases. Interestingly, molecular docking studies have demonstrated that TQ can potentially inhibit the development of the coronavirus disease 2019 (COVID-19) by binding to the receptor site on the transmembrane serine protease 2 (the activator enzyme that attaches the virus to the cell). In addition, TQ has been shown to be effective against cancer cells due to its inhibitory effect by binding to the different regions of MDM2, according to the proposed molecular docking study. Detailed in this review is the origin of TQ, its significance in alternative medicine, pharmacological value, potential as a cancer antiproliferative agent, use against the coronavirus disease 2019 (COVID-19) and for treatment of other diseases.

Coronavirus disease (CoVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) scrambles the world by infecting millions of peoples all over the globe. It has caused tremendous morbidity, mortality and greatly impacted the lives and economy worldwide as an outcome of mandatory quarantines or isolations. Despite the worsening trends of COVID-19, no drugs are validated to have significant efficacy in the clinical treatment of COVID-19 patients in large-scale studies. Physicians and researchers throughout the world are working to understand the pathophysiology to expose the conceivable handling regimens and to determine the effective vaccines and/or therapeutic agents. Some of them re-purposed drugs for clinical trials which were primarily known to be effective against the RNA viruses including MERS-CoV and SARS-CoV-1. In the absence of a proven efficacy therapy, the current management use therapies based on antivirals, anti-inflammatory drugs, convalescent plasma, anti-parasitic agents in both oral and parenteral formulation, oxygen therapy, and heparin support. What is needed at this hour, however, is a definitive drug therapy or vaccine. Different countries are rushing to find this, and various trials are already underway. We aimed to summarize the potential therapeutic strategies as treatment options for COVID-19 that could be helpful to stop further spread of SARS-CoV-2 by affecting its structural components or modulation of immune response and discuss the leading drugs/vaccines, which are considered as potential agents for controlling this pandemic.

The therapeutic potential of the majority of the marketed drugs is due to the presence of a heterocyclic nucleus, which constitutes a huge role in the field of medicinal chemistry. These heterocyclic scaffolds could act as a template in order to design potential therapeutic agents against several diseases. Benzothiazole scaffold is one of the influential heteroaromatic rings in the field of medicinal chemistry owing to its extensive pharmacological features. Herein, we have focused on the synthesis of benzothiazole-based medicinal molecules, which possess antimicrobial and anti-inflammatory activities. This review covers a systematic description of synthetic routes for biologically relevant benzothiazole derivatives in the last five years. The main aim of this study is to show the diversification of benzothiazole-based molecules into their pharmacologically more active derivatives. This review's synthetic protocols include metal-free, metal-catalyzed, and metal precursor azo dyes strategies for the development of benzothiazole derived bioactive compounds. The discussion under the various headings covers synthetic schemes and biological activities of the most potent molecules in the form of minimum inhibitory concentration.