Current Topics in Medicinal Chemistry - Volume 25, Issue 18, 2025

Autophagy is a crucial mechanism that maintains cellular homeostasis and has emerged as a pivotal factor in cancer progression and drug resistance. Despite autophagic regulations being a complex process, convincing evidence shows that PI3K-Akt-mTOR, LKB1-AMPK-mTOR, and p53 pathways are the primary upstream regulators of the autophagy process. Currently, there is an immense amount of evidence demonstrating that autophagy plays a crucial role in cancer. It is worth noting that autophagy increases cancer cells' resistance to chemotherapy and anticancerous drugs. According to studies, cancer cells employ autophagy to evade the cytotoxic impacts of several anticancer drugs, resulting in autophagy-mediated drug resistance. This resistance brings a significant challenge to cancer management, emphasising the need for improved therapeutic strategies to overcome this obstacle and enhance the efficacy of cancer treatments. Therefore, this review gathers current data and findings to understand the intricate mechanism between autophagy-mediated drug resistance and cancer progression. Moreover, this study highlights the intriguing role of natural compounds and nano-formulations in combating autophagy-mediated drug resistance in various carcinomas, presenting a promising avenue for the effective management of cancer treatment.

Nipah virus (NiV), a member of the Paramyxoviridae family, has gained global attention owing to its high mortality rate and destructive potential. NiV has a Biosafety Level 4 (BSL-4) rating and has repeatedly precipitated devastating outbreaks associated with severe respiratory infections, often accompanied by encephalitis and systemic vasculitis. Several studies have been conducted to understand the mechanisms involved in its pathogenesis and to effectively produce new medications to treat this zoonotic virus. However, the cruelty of NiV and its propensity to elude existing treatments underscores the need to elucidate better therapeutics to manage NiV infection more effectively. Therefore, this review highlights the fundamental mechanisms involved in the etiology of NiV, specifically fatal encephalitis and systemic vasculitis. Furthermore, this study investigated promising therapeutic strategies to mitigate the clinical consequences of NiV infections.

Anti-angiogenic therapy represents a promising approach to cancer treatment by targeting the vascular support systems of tumors rather than the tumor cells themselves. Antiangiogenic agents face numerous obstacles that impede their efficacy, notwithstanding their potential: mechanistic complexity, toxicity, resistance, and the lack of validated predictive biomarkers. Resistance mechanisms may encompass genetic modifications, alternative angiogenic pathways, or the recruitment of cells derived from bone marrow. This work examines present problems and approaches to overcome resistance against anti-angiogenic treatment. Treatment response is predicted by biomarker-guided therapy; patterns of circulating endothelial cells, IL-8 levels, and VEGFR expression indicate possible therapeutic monitoring value. Multi-targeted approaches including drugs that block VEGFR, PDGFR, FGFR, and c-MET concurrently have shown more efficacy than single-pathway inhibition. Additional research indicates that combining treatments has positive results. Combining anti-angiogenic agents with cancer vaccines increases immune responses and tumour regulation. Combining radiotherapy with chemotherapy increases drug delivery and efficacy utilizing vascular normalisation. Techniques based on nanotechnology such as gold nanoparticles and carbon-based materials may enhance medicinal efficacy and delivery. These results reveal that to overcome resistance mechanisms and enhance patient outcomes anti-angiogenic therapy must combine focused therapies with precision medicine approaches.

A neurohormone with strong central nervous system activity, melatonin plays a role in regulating circadian rhythms. It affects practically all tissues and organs and has a broad functional repertoire. It is primarily employed as a dietary supplement; melatonin aids in sleep regulation and the re-establishment of arousal cycles. Despite having very low toxicity, melatonin's tissue availability is constrained by pharmacokinetic problems such as poor oral bioavailability and a brief half-life. The synthesis and medicinal applications of melatonin and its derivatives are the main focus of this review study. Melatonin is considered as a beneficial agent suitable for safely treating and preventing various health conditions. This review covers synthesis approaches and pharmacological applications of melatonin and its derivatives published from the 1990s to 2024. The latest development in several studies involves the concurrent administration of melatonin with other drugs to enhance therapeutic effectiveness and mitigate adverse effects. Hybrid ligands, such as melatonin-tamoxifen and melatonin-tacrine derivatives are combined to give distinct effects. This review highlights the importance of continued research into melatonin and its derivatives, paving the way for developing novel and more potent therapeutic agents.