A Panoramic Review of Benzimidazole Derivatives and Their Potential Biological Activity

The therapeutic potential of the benzimidazole nucleus dates back to 1944, being and important heterocycle system due to its presence in a wide range of bioactive compounds such as antiviral, anticancer, antibacterial, and so on, where optimization of substituents in this class of pharmacophore has resulted in many drugs. Its extensive biological activity is due to its physicochemical properties like hydrogen bond donor-acceptor capability,  stacking interactions, coordination bonds with metals as ligands and hydrophobic interactions; properties that allow them to easily bind with a series of biomolecules, including enzymes and nucleic acids, causing a growing interest in these types of molecules. This review aims to present an overview to leading benzimidazole derivatives, as well as to show the importance of the nature and type of substituents at the N1, C2, and C5(6) positions, when they are biologically evaluated, which can lead to obtaining potent drug candidate with significant range of biological activities.

Thymoquinone: A Review of Pharmacological Importance, Oxidative Stress, COVID-19, and Radiotherapy

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 proteinase 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 anti-proliferative agent, use against the coronavirus disease 2019 (COVID-19), and treatment of other diseases.

Tuberculosis, BCG Vaccination and COVID-19: Are They Connected?

Evidence from multiple scientific studies suggests that the Bacillus Calmette–Guérin (BCG) vaccine, widely used worldwide as a preventive measure against tuberculosis, also offers cross-protection against other pathogens. This review aimed to gather data from research that studied the mechanisms involved in the immunological protection induced by the BCG vaccine, which may be important in the control of viral infections, such as COVID-19. Through a literature review, we compiled information about the different BCG strains used worldwide, as well as the responses and protection elicited by them. We commented on the mechanisms of immune response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and we discussed the possibility of cross-protection of different BCG strains on the control of COVID-19. Due to the immunomodulatory properties of BCG, some BCG strains were able to induce an effective cellular immune response and, through epigenetic modifications, activate cells of the innate immune system, such as monocytes, macrophages and natural killer cells, which are crucial for the control of viral infections. Although several vaccines have already been developed and used in an attempt to control the COVID-19 pandemic, some BCG vaccine strains may help stimulate the basal defences against these pathogens and can be used as additional defences in this and future pandemics.

Imidazole: Multi-targeted Therapeutic Leads for the Management of Alzheimer’s Disease

Background: Alzheimer's disease (AD) is a multifactorial disorder coupled with an array of neuropathological mechanisms, including tau phosphorylation, Aβ aggregation, metal ion deregulation, and oxidative stress, along with neuro-inflammation. The clinically available drugs for the management of AD include four acetylcholinesterase inhibitors and one glutamatergic antagonist. These agents provide only temporary relief from the symptoms by altering the neurotransmitter level in the brain. Objective: Keeping in view the focus on research, the numerous pharmacological activities associated with the aromatic diazole heterocyclic nucleus, imidazole, triggered the medicinal chemist to develop a large number of novel anti-AD compounds targeting multiple pathological mechanisms associated with AD. These prepared analogs represent a higher potential against neurological disorders, including AD. This review article aims an ornately pronounce the therapeutic voyage of imidazole and its analogs as anti-AD. Method: It emphasizes the synthesized imidazole derivatives as anti–AD with multiple targets reviewed from the data available on Pubmed. Result: These compounds diminish the pathophysiological aspects of AD; still, further studies are required to prove the safety and efficacy of these compounds in humans. Conclusion: The review aims to provide knowledge and highlight the status of this moiety in the design and development of novel drug candidates against Alzheimer’s disease conditions. Thus, it paves the way for further work.

Dietary Intake of Hydrolyzable Tannins and Condensed Tannins to Regulate Lipid Metabolism

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 natural derived plant, 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.

Inhibitory Activities of Pyrazolo-Oxazine Heterocyclic Derivatives

Despite several reports and reviews addressing the biological significance of pyrazoles and oxazines, no comprehensive work on the pyrazolo oxazine fused ring system has been published so far.We report all biological evaluations on pyrazolo-oxazine derivatives in this mini-review to provide an avenue for medicinal and pharmacological researchers to conduct further in-depth exploration.

An Update on Arginase Inhibitors and Inhibitory Assays

Arginase, which converts arginine into ornithine and urea, is a promising therapeutic target. Arginase is involved in cardiovascular diseases, parasitic infections and, through a critical role in immunity, in some cancers. There is a need to develop effective arginase inhibitors and therefore efforts to identify and optimize new inhibitors are increasing. Several methods of evaluating arginase activity are available, but few directly measure the product. Radiometric assays need to separate urea and dying reactions require acidic conditions and sometimes heating. Hence, there are a variety of different approaches available, and each approach has its own limits and benefits. In this review, we provide an update on arginase inhibitors, followed by a discussion on available arginase assays and alternative methods, with a focus on the intrinsic biases and parameters that are likely to impact results.

Discovery and Development of Antibacterial Agents: Fortuitous and Designed

Today, antibacterial drug resistance has turned into a significant public health issue. Repeated intake, suboptimal and/or unnecessary use of antibiotics, and, additionally, the transfer of resistance genes are the critical elements that make microorganisms resistant to conventional antibiotics. A substantial number of antibacterials that were successfully utilized earlier for prophylaxis and therapeutic purposes have been rendered inadequate due to this phenomenon. Therefore, the exploration of new molecules has become a continuous endeavour. Many such molecules are at various stages of investigation. A surprisingly high number of new molecules are currently in the stage of phase 3 clinical trials. A few new agents have been commercialized in the last decade. These include solithromycin, plazomicin, lefamulin, omadacycline, eravacycline, delafloxacin, zabofloxacin, finafloxacin, nemonoxacin, gepotidacin, zoliflodacin, cefiderocol, BAL30072, avycaz, zerbaxa, vabomere, relebactam, tedizolid, cadazolid, sutezolid, triclosan and afabiacin. This article aims to review the investigational and recently approved antibacterials with a focus on their structure, mechanisms of action/resistance, and spectrum of activity. Delving deep, their success or otherwise in various phases of clinical trials is also discussed while attributing the same to various causal factors.