Current Topics in Medicinal Chemistry - Volume 23, Issue 7, 2023

Despite great efforts in the discovery of antifungal drugs in the last two decades, the increasing incidence of infectious diseases from diverse pathogenic fungi threatens public healthcare and medical sector. Particularly, the invasive infection caused by the yeast Candida Albicans in immunocompromised patients has been widely reported with 25-55% of mortality rate. The major concerns faced by the use of current antifungal agents are the development of fungal resistance, side effects, toxicity, narrow spectrum of fungal activity, and constraints in the route of administration. However, among the four known classes of antifungal drugs currently used in therapy against invasive fungal infections, only one novel antifungal class has been approved by the FDA in 2021 for medical use. In addition, two derivatives with the identification of their corresponding novel molecular targets are currently in the last phase of clinical trial. In this context, the discovery of novel compounds with potential antifungal activity needs to be explored urgently in order to address these concerns. Among various heterocycles, benzothiazole presents a privileged scaffold for developing bio-active compounds with a broad spectrum of pharmacological activities. Many derivatives incorporating the benzothiazole core have been reported to display prominent activity against a variety of non-resistant and resistant fungal microorganisms and have been found to be very attractive for the development of novel antifungal agents. Therefore, in this review, the latest advances in the discovery of benzothiazole-containing antifungal agents are summarized with an emphasis on their spectrum of activity and their structure-activity relationship. We hope that this study will provide researchers structural insight into antifungal molecules for the development of the next generation of antifungal drugs.

Viral infections range from self-limiting to more serious and fatal infections; therefore, some viral infections are of great public health concern worldwide, e.g., Hepatitis B virus, Hepatitis C virus, and HIV. Recently, the world faced a new infection due to the coronavirus, COVID-19, which was announced as a pandemic in early 2020. This virus infected more than 500 million people, killing around 6 million people worldwide. On the other hand, the increase in drug-resistant strains is also creating serious health problems. Thus, developing new selective antiviral agents with a different mode of action to fight against mutated and novel viruses is a primary goal of many researchers. Taking into account the role of heterocyclic compounds in drug discovery as a key structural component of most of the bioactive molecules; herein, we report an extensive review of the antiviral activity of five-membered heterocyclic compounds reported from 2015 to date. In this review, the antiviral activities of the agents containing the specified ring systems thiadiazoles, triazoles, oxadiazoles, and thiazoles are discussed.

Eukaryotic cells have separate membrane-enclosed organelles with distinct biochemical identities and specialized functions. The unique characteristics of each organelle are regulated by asymmetric distribution and intra-cellular trafficking of two important biomolecules, proteins and lipids. Non-vesicular lipid transport facilitated by lipid transfer proteins performs essential roles in intracellular lipid trafficking and homeostasis, while vesicular transport regulates protein trafficking. Comparative analysis of lipid transport machinery in protists could help us to understand the basis of parasitism and insight into eukaryotic evolution. Trichomonas vaginalis, a parasitic protist, greatly depends on receptor-ligand-mediated signaling pathways for cellular differentiation, nutrient uptake, secretion of virulence factors, and pathogenesis. Lipids, despite being key molecules of signaling cascades, have mechanisms of intracellular transport that are largely unexplored in T. vaginalis. We have identified a repertoire of seventeen potential lipid transfer protein (LTP) homologs in T. vaginalis based on a domain-based search on TrichDB (genome database of Trichomonas) coupled with bioinformatics analyses, which indicates the presence of well-organized lipid transport machinery in this parasite. We emphasized here their evolutionary uniqueness and conservation and discussed their potential implications for parasite biology in regard to future therapeutic targets against Trichomoniasis.

Malaria is one of the neglected infectious diseases, and drugs are the first line of action taken against the onset of malaria as therapeutics. The drugs can be of either natural or artificial origin. Drug development has multiple impediments grouped under three categories, a. drug discovery and screening, b. the drug's action on the host and the pathogen, and c. clinical trials. Drug development takes coon’s age from discovery to the market after FDA approval. At the same time, targeted organisms develop drug resistance quicker than drug approval, raising the requirement for advancement in drug development. The approach to explore drug candidates using the classical methods from natural sources, computation-based docking, mathematical and machine learningbased high throughput in silico models or drug repurposing has been investigated and developed. Also, drug development with information about the interaction between Plasmodium species and its host, humans, may facilitate obtaining an efficient drug cohort for further drug discovery or repurposing expedition. However, drugs may have side effects on the host system. Hence, machine learning and systems-based approaches may provide a holistic view of genomic, proteomic, and transcriptomic data and their interaction with the selected drug candidates. This review comprehensively describes the drug discovery workflows using drug and target screening methodologies, followed by possible ways to check the binding affinity of the drug and targets using various docking software.

Despite breakthroughs in medical sciences, drug development remains a timeconsuming, expensive, challenging, and inefficient process with a high failure rate for novel therapeutic discoveries. Bioinformatics analysis can speed up drug target identification, drug candidate screening, and refining, but it can also help characterise adverse effects and anticipate drug resistance. Integrated genomics, proteomics, and bioinformatics have resulted in potent new tactics for resolving numerous biochemical problems and establishing new methodologies that result in new biomedical products. As a result, a new research trend emerged to demonstrate the mechanism of therapeutic action, forecast drug resistance, and uncover biomarkers for various disorders. The development of new medications is a complicated procedure. There are two basic approaches to drug design: ligand-based drug design and structure-based drug design. The study of protein structure and function was essential for drug development. Current techniques based on combinatorial approaches such as proteomics, genomics, bioinformatics, molecular docking, and mass spectrometry were applied. This article provides an overview of the combinatorial techniques of proteomics, genomics, and bioinformatics that aid in understanding the drug-creation process.