Mini Reviews in Medicinal Chemistry - Volume 24, Issue 3, 2024

Coronavirus disease-19 (COVID-19), a serious pandemic due to the SARS-CoV-2 virus infection, caused significant lockdowns, healthcare shortages, and deaths worldwide. The infection leads to an uncontrolled systemic inflammatory response causing severe respiratory distress and multiple-organ failure. Quick development of several vaccines efficiently controlled the spread of COVID-19. However, the rise of various new subvariants of COVID-19 demonstrated some concerns over the efficacy of existing vaccines. Currently, better vaccines to control these variants are still under development as several new subvariants of COVID-19, such as omicron BA-4, BA-5, and BF-7 are still impacting the world. Few antiviral treatments have been shown to control COVID-19 symptoms. Further, control of COVID-19 symptoms has been explored with many natural and synthetic adjuvant compounds in hopes of treating the deadly and contagious disease. Vitamins have been shown to modulate the immune system, function as antioxidants, and reduce the inflammatory response. Recent studies have investigated the potential role of vitamins, specifically vitamins A, B, C, D, and E, in reducing the immune and inflammatory responses and severity of the complication. In this brief article, we discussed our current understanding of the role of vitamins in controlling COVID-19 symptoms and their potential use as adjuvant therapy.

Coronavirus disease 2019 (COVID-19) affects thyroid function. These changes are due to the direct impact of the virus on thyroid cells via angiotensin-converting–enzyme 2 (ACE2) receptors, inflammatory reaction, apoptosis in thyroid follicular cells, suppression of hypothalamus-pituitarythyroid axis, an increase in activity of adrenocortical axis, and excess cortisol release due to cytokine storm of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Euthyroid sick syndrome (ESS), thyroiditis, clinical and subclinical hypothyroidism, central hypothyroidism, exacerbation of underlying autoimmune thyroid disease, and clinical and subclinical hyperthyroidism can be associated with coronavirus. Adjuvants in coronavirus vaccines induce autoimmune/inflammatory syndrome known as vaccine adjuvants (ASIA) syndrome. Thyroiditis and Graves’ disease have been reported to be associated with ASIA syndrome after some coronavirus vaccinations. Some coronavirus medications, such as hydroxychloroquine, monoclonal antibodies, lopinavir/ritonavir, remdesivir, naproxen, anticoagulants, and glucocorticoids can also affect thyroid tests, and correct diagnosis of thyroid disorders will be more difficult. Changes in thyroid tests may be one of the most important manifestations of COVID-19. These changes can be confusing for clinicians and can lead to inappropriate diagnoses and decisions. Prospective studies should be conducted in the future to increase epidemiological and clinical data and optimize the management of thyroid dysfunctions in patients with COVID-19.

Wounds provide a favourable site for microbial infection. Wound infection makes the healing more complex and does not proceed in an orchestrated manner leading to the chronic wound. Clinically infected wounds require proper antimicrobial therapy. Broad-spectrum antibiotics are usually prescribed first before going to targeted therapy. The current conventional mode of therapy mainly depends on the use of antibiotics topically or systemically. Repeated and prolonged use of antibiotics, however, leads to multidrug resistance. Staphylococcus aureus is the most common multidrugresistant microorganism found in wounds. It effectively colonizes the wound and produces many toxins, thereby reducing the host immune response and causing recurrent infection, thus making the wound more complex. The overexpression of efflux pumps is one of the major reasons for the emergence of multidrug resistance. Inhibition of efflux pumps is, therefore, a potential strategy to reverse this resistance. The effective therapy to overcome this antibiotic resistance is to use combination therapy, namely the combination of an inhibitor, and a non-antibiotic compound with an antibiotic for their dual function. Many synthetic efflux pump inhibitors to treat wound infections are still under clinical trials. In this connection, several investigations have been carried out on plant-based natural products as multidrug resistance-modifying agents as they are believed to be safe, inexpensive and suitable for chronic wound infections.

Alongside the prescription of commonly used antivirals, such as acyclovir, remdesivir, oseltamivir, and ciprofloxacin, the most efficient way to prevent or treat communicable diseases is by vaccination. Vaccines have been the most efficient way to prevent or treat highly transmissible infectious agents, such as Ebola, Anthrax, and Dengue Fever. Most epidemics of these highly transmissible infectious agents occur in places, such as South America, Central America, Tropical Asia, and Africa, where the availability of resources and access to adequate healthcare are limited. However, recent events in history have proven that even with access to resources and proper healthcare, those in firstworld countries are not invincible when it comes to infectious diseases and epidemics. The Ebola virus outbreak in West Africa highlighted the gaps in therapeutic advancement and readiness and led to the rapid development of novel vaccine approaches. Viral vectors, in the case of the Ebola vaccine the Vesicular Stomatitis Virus (VSV), can be safely used to activate or initiate the innate adaptive immune response to protect against viral infection. When developed properly and with extensive study, novel vaccine approaches allow physicians and health experts to control the rate at which viruses spread or prevent transmission. This review will discuss the advantages of viral vector vaccines, their chemistry and development, and the pathophysiology of the Ebola virus to develop advantageous and efficacious treatments.

Three gaseous molecules are widely accepted as important gasotransmitters in mammalian cells, namely NO, CO and H2S. Due to the pharmacological effects observed in preclinical studies, these three gasotransmitters represent promising drug candidates for clinical translation. Fluorescent probes of the gasotransmitters are also in high demand; however, the mechanisms of actions or the roles played by gasotransmitters under both physiological and pathological conditions remain to be answered. In order to bring these challenges to the attention of both chemists and biologists working in this field, we herein summarize the chemical strategies used for the design of both probes and prodrugs of these three gasotransmitters.

Background: The structure–property relationship illustrates how modifying the chemical structure of a pharmaceutical compound influences its absorption, distribution, metabolism, excretion, and other related properties. Understanding structure–property relationships of clinically approved drugs could provide useful information for drug design and optimization strategies.Method: Among new drugs approved around the world in 2022, including 37 in the US, structure– property relationships of seven drugs were compiled from medicinal chemistry literature, in which detailed pharmacokinetic and/or physicochemical properties were disclosed not only for the final drug but also for its key analogues generated during drug development.Results: The discovery campaigns for these seven drugs demonstrate extensive design and optimization efforts to identify suitable candidates for clinical development. Several strategies have been successfully employed, such as attaching a solubilizing group, bioisosteric replacement, and deuterium incorporation, resulting in new compounds with enhanced physicochemical and pharmacokinetic properties.Conclusion: The structure-property relationships hereby summarized illustrate how proper structural modifications could successfully improve the overall drug-like properties. The structure–property relationships of clinically approved drugs are expected to continue to provide valuable references and guides for the development of future drugs.

Purpose: Diabetes is one of the important and growing diseases in the world. Among the most common diabetic complications are renal adverse effects. The use of apigenin may prevent the development and progression of diabetes-related injuries. The current study aims to review the effects of apigenin in the treatment of diabetic nephropathy.Methods: In this review, a systematic search was performed based on PRISMA guidelines for obtaining all relevant studies on "the effects of apigenin against diabetic nephropathy" in various electronic databases up to September 2022. Ninety-one articles were obtained and screened in accordance with the predefined inclusion and exclusion criteria. Seven eligible articles were finally included in this review.Results: The experimental findings revealed that hyperglycemia led to the decreased cell viability of kidney cells and body weight loss and an increased kidney weight of rats; however, apigenin administration had a reverse effect on these evaluated parameters. It was also found that hyperglycemia could induce alterations in the biochemical and renal function-related parameters as well as histopathological injuries in kidney cells or tissue; in contrast, the apigenin administration could ameliorate the hyperglycemia-induced renal adverse effects.Conclusion: The results indicated that the use of apigenin could mitigate diabetes-induced renal adverse effects, mainly through its antioxidant, anti-apoptotic, and anti-inflammatory activities. Since the findings of this study are based on experimental studies, suggesting the use of apigenin (as a nephroprotective agent) against diabetic nephropathy requires further clinical studies.

Background: Metabolic syndrome (METS) is a set of unhealthy medical conditions considered essential health problems today. Cinnamaldehyde (CA) is the major phytochemical present in the essential oil of cinnamon and possesses antioxidant, anti-inflammatory, hypoglycemic, and antihyperlipidemic activities.Aim: We aim to systematically review the effects of CA in preventing and attenuating METS components. Moreover, the cellular and molecular mechanisms of actions of CA, its pharmacokinetics features, and potential structure-activity relationship (SAR) were also surveyed.Methods: PubMed, Science Direct, Scopus, and Google Scholar were searched to retrieve the relevant papers.Results: CA possesses various anti-METS activities, including anti-inflammatory, antioxidant, antidiabetic, antidyslipidemia, antiobesity, and antihypertensive properties. Various molecular mechanisms such as stimulating pancreatic insulin release, exerting an insulinotropic effect, lowering lipid peroxidation as well as pancreatic islet oxidant and inflammatory toxicity, increasing the activities of pancreatic antioxidant enzymes, suppressing pro-inflammatory cytokines production, regulating the molecular signaling pathways of the PPAR-γ and AMPK in preadipocytes and preventing adipocyte differentiation and adipogenesis are involved in these activities.Conclusions: CA would effectively hinder METS; however, no robust clinical data supporting these effects in humans is currently available. Accordingly, conducting clinical trials to evaluate the efficacy, safe dosage, pharmacokinetics characteristics, and possible unwanted effects of CA in humans would be of great importance.