Current Pharmaceutical Design - Volume 32, Issue 12, 2026

Genetic factors play a significant role in the development of leukemia. The overexpression of MDM2 is associated with the progression of certain leukemias. This meta-analysis investigates the relationship between the MDM2 SNP 309T>G and various forms of leukemia across global populations.

A comprehensive literature search was conducted to retrieve genotyping data from twenty case-control studies related to MDM2 SNP 309T>G polymorphism and leukemia. A random-effects model was used to calculate the pooled odds ratio (OR) and 95% confidence interval (95% CI) for the association analysis. MetaGenyo software was utilized to conduct statistical analyses in this meta-analysis.

The findings indicate a significant association between MDM2 309 SNPT>G polymorphism and leukemia in Asian and Caucasian populations. Additionally, this polymorphism is associated with an increased risk of Acute Myeloid Leukemia (AML) and Chronic Myeloid Leukemia (CML), implying that MDM2 may play a role in the pathogenesis of these specific forms of leukemia.

This meta-analysis suggests that MDM2 may represent a susceptibility gene for leukemia risk.

The COVID-19 pandemic, caused by SARS-CoV-2, has highlighted the urgent need for effective antiviral and anti-inflammatory therapies. Spiropyridine derivatives containing a chalcone moiety have shown potential in targeting key enzymes involved in viral replication and inflammation.

To evaluate the inhibitory effects of synthesized spiropyridine derivatives on SARS-CoV-2 main protease (Mpro), secreted phospholipase A2 (sPLA2), and cytosolic phospholipase A2 (cPLA2), and to assess their impact on inflammatory and oxidative stress markers in LPS-treated lung cells.

To develop novel therapeutic agents that can effectively manage COVID-19 and related inflammatory conditions.

The synthesized compounds (1-3) were tested for their inhibitory activity against SARS-CoV-2 Mpro, sPLA2, and cPLA2 using in vitro assays to determine IC50 values. Inflammatory markers (COX-2, IL-2, IL-4, TGF-1β, TNF-α) and oxidative stress markers (GSH, SOD, GR, MDA) were measured in LPS-treated lung cells. Gene expression levels of sPLA2 and cPLA2 were also assessed. Molecular docking studies were conducted to analyze the binding affinities and interactions of the compounds with the target enzymes.

Compounds 1-3 showed significant inhibitory activity against SARS-CoV-2 Mpro with IC50 values of 19.85 µM, 7.31 µM, and 3.73 µM, respectively. For comparison, baicalein's IC50 value was 13.63 µM. Additionally, these compounds inhibited sPLA2 with IC50 values of 8.36 µM, 7.31 µM, and 3.73 µM, and cPLA2 with IC50 values of 20.44 µM, 6.02 µM, and 4.61 µM, respectively. Baicalein's IC50 values for sPLA2 and cPLA2 were 11.73 µM and 5.89 µM, respectively. In LPS-treated lung cells, compounds 1-3 significantly reduced COX-2 by up to 90.12%, IL-2 by 74.19%, IL-4 by 79.51%, TGF-1β by 44.57%, and TNF-α by 68.49%. They enhanced GSH by up to 194%, SOD by 357.19%, and GR by 445.87%, while reducing MDA by 77.90%. Gene expression of sPLA2 and cPLA2 was significantly downregulated by up to 82.31% and 64.59%, respectively. Molecular docking studies revealed binding affinities of -28.20, -28.20, and -28.07 kcal/mol for SARS-CoV-2 Mpro; -16.72, -17.21, and -15.89 kcal/mol for sPLA2; and -65.66, -66.95, and -79.24 kcal/mol for cPLA2, respectively.

The results demonstrate that the structural integration of a spiropyridine core with a chalcone moiety yields compounds with superior multi-target inhibitory activity. The potent antiviral, anti-inflammatory, and antioxidant effects are significantly correlated with their strong binding interactions with the active sites of Mpro, sPLA2, and cPLA2, as validated by molecular docking. These findings align with and extend current research on targeting host-inflammatory pathways alongside viral replication for COVID-19 management.

The synthesized spiropyridine derivatives containing a chalcone moiety exhibit potent antiviral, anti-inflammatory, and antioxidant properties. These findings suggest that these compounds could be promising therapeutic agents for managing COVID-19 and related inflammatory conditions. Future studies should focus on in vivo experiments, clinical trials, and structural optimization to further develop these compounds for clinical use.