Mini Reviews in Medicinal Chemistry - Volume 24, Issue 14, 2024

Medicinal insects play an important role in the treatment of refractory diseases due to their unique and rich pharmacological activities. However, compared to plants, microorganisms, and marine organisms, medicinal insects have been largely ignored. Some small molecules isolated from insects are known to have defensive effects, but their majority roles remain unknown. In-depth research on the small molecules of medicinal insects has been conducted in recent years. Then alkaloids, dopamine derivatives, nucleoside derivatives, and other components are obtained. Among them, dopamine derivatives are a unique class of components from medicinal insects. Thus, we present a comprehensive overview of chemical structures and biological activities of dopamine derivatives from some medicinal insects, which will bring more attention to other researchers for further chemical and biological investigations on the unique dopamine derivatives as well as medicinal insects.

Rational predictions on binding kinetics parameters of drugs to targets play significant roles in future drug designs. Full conformational samplings of targets are requisite for accurate predictions of binding kinetic parameters. In this review, we mainly focus on the applications of enhanced sampling technologies in calculations of binding kinetics parameters and residence time of drugs. The methods involved in molecular dynamics simulations are applied to not only probe conformational changes of targets but also reveal calculations of residence time that is significant for drug efficiency. For this review, special attention are paid to accelerated molecular dynamics (aMD) and Gaussian aMD (GaMD) simulations that have been adopted to predict the association or disassociation rate constant. We also expect that this review can provide useful information for future drug design.

Background: Uncontrolled cell growth and proliferation, which originate from lung tissue often lead to lung carcinoma and are more likely due to smoking as well as inhaled environmental toxins. It is widely recognized that tumour cells evade the ability of natural programmed death (apoptosis) and facilitates tumour progression and metastasis. Therefore investigating and targeting the apoptosis pathway is being utilized as one of the best approaches for decades. Objective: This review describes the emergence of SMAC mimetic drugs as a treatment approach, its possibilities to synergize the response along with current limitations as well as future perspective therapy for lung cancer. Method: Articles were analysed using search engines and databases namely Pubmed and Scopus. Result: Under cancerous circumstances, the level of Inhibitor of Apoptosis Proteins (IAPs) gets elevated, which suppresses the pathway of programmed cell death, plus supports the proliferation of lung cancer. As it is a major apoptosis regulator, natural drugs that imitate the IAP antagonistic response like SMAC mimetic agents/Diablo have been identified to trigger cell death. SMAC i.e. second mitochondria activators of caspases is a molecule produced by mitochondria, stimulates apoptosis by neutralizing/inhibiting IAP and prevents its potential responsible for the activation of caspases. Various preclinical data have proven that these agents elicit the death of lung tumour cells. Apart from inducing apoptosis, these also sensitize the cancer cells toward other effective anticancer approaches like chemo, radio, or immunotherapies. There are many SMAC mimetic agents such as birinapant, BV-6, LCL161, and JP 1201, which have been identified for diagnosis as well as treatment purposes in lung cancer and are also under clinical investigation. Conclusion: SMAC mimetics acts in a restorative way in the prevention of lung cancer.

Drug discovery is a complex and iterative process, making it ideal for using artificial intelligence (AI). This paper uses a bibliometric approach to reveal AI's trend and underlying structure in drug discovery (AIDD). A total of 4310 journal articles and reviews indexed in Scopus were analyzed, revealing that AIDD has been rapidly growing over the past two decades, with a significant increase after 2017. The United States, China, and the United Kingdom were the leading countries in research output, with academic institutions, particularly the Chinese Academy of Sciences and the University of Cambridge, being the most productive. In addition, industrial companies, including both pharmaceutical and high-tech ones, also made significant contributions. Additionally, this paper thoroughly discussed the evolution and research frontiers of AIDD, which were uncovered through co-occurrence analyses of keywords using VOSviewer. Our findings highlight that AIDD is an interdisciplinary and promising research field that has the potential to revolutionize drug discovery. The comprehensive overview provided here will be of significant interest to researchers, practitioners, and policy-makers in related fields. The results emphasize the need for continued investment and collaboration in AIDD to accelerate drug discovery, reduce costs, and improve patient outcomes.

Usnic acid has a variety of biological activities, and has been widely studied in the fields of antibacterial, immune stimulation, antiviral, antifungal, anti-inflammatory and antiparasitic. Based on this, usnic acid is used as the lead compound for structural modification. In order to enhance the biological activity and solubility of usnic acid, scholars have carried out a large number of structural modifications, and found some usnic acid derivatives to be of more potential research value. In this paper, the structural modification, biological activity and structure-activity relationship of usnic acid were reviewed to provide reference for the development of usnic acid derivatives.