Mini Reviews in Medicinal Chemistry - Volume 25, Issue 3, 2025

Most of the antiviral drugs in the market are designed to target viral proteins directly. They are generally considered safe for human use. However, they also suffer from several inherent limitations, in particular, narrow-spectrum antiviral profiles and liability to drug resistance. The other strategy for antiviral drug development is targeting host factors, which are highly involved at different stages in the viral life cycle. In contrast to direct-acting antiviral agents, host-targeting antiviral ones normally exhibit broad-spectrum antiviral properties along with a much higher genetic barrier to drug resistance. Cyclin-dependent kinases (CDKs) represent one such host factor. In this review, we summarized a number of CDK inhibitors (CDKIs) of varied chemical scaffolds with demonstrated antiviral activity. Challenges and issues associated with the repurposing of CDKIs as antiviral agents were also discussed.

Finding the most perfect drug candidates in the fields of drug discovery and medicinal chemistry will remain the main interest of drug designers. This concern necessitates organic and medicinal chemists, in most examples, to precisely design and search for drug candidates that are very analogous to the present effective drugs with solving, mainly, their proven critical pharmacological and clinical issues through slightly changing one or two atoms of the principal functional skeletons of the molecules of these present therapeutics by atom swapping, removal, and/or addition procedures in organic chemical synthesis. This accurate modern chemicosimilarity tactic in drug discovery surely saves time while keeping us very close, or sometimes highly superior, to the parent pharmacophoric bioactivity (i.e., keeping considerable analogy to the parent therapeutic molecule). From this perspective and logic, the science of skeletal editing of molecules (i.e., skeletal molecular editing) arose in the era of artificial intelligence (AI) and its dramatic predictions. As a pioneer in this modern branch in pharmaceutical and therapeutic organic chemistry, in this up-to-date minireview and perspective article, an attempt was made to introduce skeletal editing and its synthetic surgeries (over molecules) to the audience (including irrelevant readers) in a simpler and more attractive way as a novel chemical technology, highlighting the previous synthetic trials (in general), demonstrating the three main techniques, and, finally, discussing the future therapeutic needs and scenarios from a medicinal chemist's viewpoint.

Flu is an acute respiratory disease caused by influenza viruses. The influenza viruses are classified as Alphainfluenzavirus (influenza A virus, IAV), Betainfluenzavirus (influenza B virus, IBV), Gammainfluenzavirus (influenza C virus, ICV), and Deltainfluenzavirus (influenza D virus, IDV) according to the antigenicity of nucleoproteins (NPs) and matrix (M) proteins in vivo. It is estimated that the seasonal influenza epidemics will cause about 3-5 million cases of serious illness and 290,000-650,000 deaths in the world every year, while influenza A virus is the leading cause of infection and death. Neuraminidase (NA) is one of the most critical targets for the development of anti-influenza virus drugs, and the main drugs clinically applied for the treatment of flu are neuraminidase inhibitors. However, various mutant strains have developed resistance to these inhibitors (For example, the substrains of H274Y in H1N1, H5N1, and E119V in H3N2 have developed resistance to Oseltamivir). Influenza viruses mutate frequently, and new substrains emerge constantly, and the pandemics caused by the new substrains will break out at any time. Therefore, it is urgent to develop new and wide-spectrum influenza virus inhibitors for overcoming the emerging influenza pandemic. Here, we focus on describing the progress of influenza virus inhibitors in clinics and clinical trials to provide a comprehensive reference for the researchers.

While the use of plants in traditional medicine dates back to 1500 B.C., modern advancements led to the development of innovative therapeutic techniques. On the other hand, in the field of anti-infective agents, lack of efficacy and the onset of resistance stimulate the search for novel agents. Genus Artemisia is one of the most diverse among perennial plants with a variety of species, properties, and chemical components. The genus is known for its therapeutic values and, in particular, for its role in the origin of antimalarial agents derived from artemisinin. In this review, we aim to provide an updated overview of the evolution of natural and nature-inspired compounds related to the genus Artemisia that have been proven, in vitro and in vivo, to possess antimalarial properties. An overview of the chemical composition and a description of the ethnopharmacological aspects will be presented, as well as an updated report on in vitro and in vivo evidence that allowed the translation of artemisinin and its derivatives from traditional chemistry into modern medicinal chemistry. The biological and structural properties will be discussed, also dedicating attention to the challenging tasks that still are open, such as the identification of optimal combination strategies, the routes of administration, and the full assessment of the mechanism of action.

This review article delves into the critical role of Enoyl acyl carrier protein reductase (InhA; ENR), a vital enzyme in the NADH-dependent acyl carrier protein reductase family, emphasizing its significance in fatty acid synthesis and, more specifically, the biosynthesis of mycolic acid. The primary objective of this literature review is to elucidate diverse scaffolds and their developmental progression targeting InhA inhibition, thereby disrupting mycolic acid biosynthesis. Various scaffolds, including thiourea, piperazine, thiadiazole, triazole, quinazoline, benzamide, rhodanine, benzoxazole, and pyridine, have been systematically explored for their potential as InhA inhibitors. Noteworthy findings highlight thiadiazole and triazole derivatives, demonstrating promising IC50 values within the nanomolar concentration range. The review offers comprehensive insights into InhA's structure, structure-activity relationships, and a detailed overview of distinct scaffolds as effective inhibitors of InhA.

Essential oils (EOs) are a volatile mixture of bioactive compounds extracted from aromatic plants. The composition of EOs varies, which majorly depends on the extraction methods and plant parts. Aromatherapy using EOs has been reported for its several beneficial effects in humans. Aromatherapy is considered a complementary and/ or adjuvant therapeutic approach for treating several illnesses, especially to improve mental health and well-being. The incidence of sleep disorders, specifically insomnia, is nowadays increased, possibly due to urbanization and lifestyle. The studies showed that EOs-based treatments using lavender EO, bergamot EO, cinnamon EO, and rosemary EO (alone or in combinations) could improve sleep quality, duration, and deprivation in healthy subjects and patients, those who suffer from sleep-related issues. The current manuscript details the outcomes of EO-based treatments on the sleep quality of humans and the possible mechanisms associated with the health-promoting properties of EOs. Also, the toxicity and adverse effects of EOs have been discussed. The study indicated that EOs are potent adjuvant therapeutic candidates to manage mood-associated complications in humans. Moreover, the aromatherapeutic field requires detailed studies on toxicity and dose determination, which could provide safe and effective therapeutic results.