Current Topics in Medicinal Chemistry - Volume 25, Issue 13, 2025

Diabetes mellitus, a metabolic disease characterized by high blood glucose levels, has increased dramatically in recent years, prompting the need for more affordable diagnoses and treatments.

This study aimed to conduct a brief historical and theoretical review on the development of insulin.

Scientific and technological data have been retrieved and analyzed with a focus on the development of the active pharmaceutical ingredient insulin and insulin-based medicines. Data have been retrieved from the PubMed database available via the CAPES portal.

Diabetes is one of the oldest diseases in the world. The year 2021 marked the 100^th anniversary of the discovery of insulin, which transformed diabetes from a fatal disease into a chronic disease. The extraction and purification of insulin from bovine or porcine pancreases from slaughterhouses has enabled the pharmaceutical industry to produce insulin on a large scale. The introduction of insulin analogs in 1996 expanded the options. Currently, commercial insulin consists of human insulin and/or human insulin analogs.

The state-of-the-art and technological development of insulin over the last 100 years has been presented in this work. The development of new pharmaceutical technologies has led to the obtainment of improved versions of insulin, as well as the emergence of different types of insulin. Alongside the innovations in the development of the active ingredient and related medicines, new formulations, methods, and routes of administration have emerged based on the pharmacodynamic, pharmacokinetic, and pharmacotechnical modulations of the drug.

A heterocyclic molecule containing five rings, three carbon atoms, two nitrogen atoms, and a single endocyclic bond is called pyrazoline. Because of its intriguing electrical characteristics and potential for dynamic applications, pyrazoline is one type of electron-rich nitrogen carrier that is becoming more and more popular. This study synthesizes pyrazoline derivatives using a variety of techniques to demonstrate a highly biological function.

Pharmaceutical chemistry has found the study of the biological activity of pyrazoline derivatives to be an interesting field. Pyrazolines find utility in numerous multipurpose applications. It has been discussed to examine the current study of patent literature on pyrazoline derivatives (2000–2024) that describes the introduction, general approach, synthesis scheme Structure-activity and relationship, marketed drug, and patents on anticancer activities.

A recognized heterocyclic chemical is pyrazolines. Three carbon atoms and two adjacent nitrogen atoms make up the five-membered ring that is pyrazoline. A variety of methods are available to determine its synthesis. Extensive studies have been conducted in this field since it has been found that many pyrazoline derivatives have a crucial biological effect on anticancer activity. The application of pyrazoline as an anticancer agent is a fascinating moiety with a wealth of potential applications for further research by scientists.

Hepatic ischemia reperfusion injury (HIRI) is a common complication closely related to the prognosis of liver surgery, and effective treatment methods are still unavailable. SRT1720 has the characteristics of multifunction and multitarget which may cope with the multidirectional complex pathological process caused by HIRI. The present study aimed to explore the potential mechanism of SRT1720 in HIRI through a combination of network pharmacology, in vitro experiments and in vivo models.

Differentially expressed genes (DEGs) were identified based on the GSE15480 and Genecards database. Enrichment analyses were then conducted. SRT1720-targeted genes were obtained through databases such as Chembl, TTD, GtoPdb, and so on. All target genes were standardized by the Uniprot database and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were identified by STRING. Shared KEGG pathways were identified using a Venn diagram among SRT1720-targeted pathways and HIRI. Furthermore, experimental techniques such as cell apoptosis assay and western blotting were used to confirm the most significant biological processes and the key pathway between SRT1720-targeted and HIRI.

This study identified 118 HIRI-related DEGs, 69 shared KEGG pathways of SRT1720 and HIRI. In addition, the findings revealed that SRT1720 significantly reduced liver ischemia-reperfusion (I/R) injury. NF-κB signaling pathway and the expression of promoting apoptosis factors such as Bax and Caspase3 were inhibited, while antiapoptotic protein Bcl-2 was promoted in the SRT1720 group compared with the I/R group.

The findings indicate that SRT1720 may inhibit the development of HIRI by inhibiting the NF-κB signaling pathway and reducing cell apoptosis, acting as a treatment for HIRI.