Mini Reviews in Medicinal Chemistry - Volume 25, Issue 21, 2025

Imidazo[2,1-b][1,3,4]thiadiazoles, a class of fused bicyclic heterocycles, have garnered significant interest in medicinal chemistry due to their diverse biological activities, particularly their anticancer properties. Over recent decades, extensive research has been conducted to explore and enhance their therapeutic potential. This comprehensive review spans six decades of research on the imidazo[2,1-b][1,3,4]thiadiazole scaffold, focusing on structural variations at C-2, C-5, and C-6 position on this scaffold and their implications for anticancer activity. Modifications at these positions have been shown to significantly impact the compound’s efficacy against various cancer cell lines. Continuous exploration and optimization of these substitutions hold promise for the development of novel anticancer therapeutics.

Musculin antisense RNA 1 (MSC-AS1) is a long non-coding RNA (lncRNA) located on human chromosome 8q13.3-q21.11. Emerging evidence shows that MSC-AS1 is either upregulated or downregulated in 16 types of human cancers, and is associated with clinical pathological features and patient prognosis in 12 of these cancers. It is widely believed that the dysregulation of MSC-AS1 contributes to tumor cell growth, metastasis, epithelial-mesenchymal transition (EMT) progression, metabolic reprogramming, and drug resistance formation. Mechanistically, MSC-AS1 can act as a competing endogenous RNA (ceRNA) by sponging 14 miRNAs to affect the expression of downstream mRNAs, or it may directly interact with proteins, both of which contribute to the activation of the PI3K/AKT and Wnt/β-catenin signaling pathways. Our review study suggests that MSC-AS1 is a potential cancer biomarker and therapeutic target. In summary, we have explained the research on MSC-AS1 related to cancer treatment, its expression patterns, functional characteristics, and molecular mechanisms in malignant tumors. We have further emphasized its significance in clinical prognosis and therapeutic applications.

The primary feature of Parkinson's disease (PD), a progressive neurodegenerative disease that results in both motor and non-motor dysfunctions, is the degeneration of dopaminergic neurons in the substantia nigra. In recent years, indole-based compounds have emerged as promising candidates for developing novel treatments for Parkinson's disease due to their diverse pharmacological properties. Among the significant pathogenic targets against which indole derivatives exhibit potent activity are monoamine oxidase (MAO), NMDA receptors, oxidative stress, and neuroinflammation. This review provides an in-depth analysis of synthetic indole derivatives as potential therapeutic agents for Parkinson’s disease. We explore how these compounds may reduce the pathology associated with Parkinson's disease, identify molecular targets, and analyze the relationships between their structure and activity. We also discuss recent advances in computational and medicinal chemistry that aim to enhance indole structures. Potential challenges and upcoming prospects for the therapeutic application of indole-based therapies are also considered in the review. The ultimate objective of this study is to elucidate the potential applications of synthetic indole derivatives in the development of innovative therapies for Parkinson's disease.