Drug-induced hepatotoxicity is one of the most commonly encountered obstacles in the field of medical practice. Sodium valproate (VPA) is among many drugs with reported hepatotoxic effects. Sulforaphane (SFN) is a thiol compound found in wide abundance in cruciferous plants that has numerous reported therapeutic efficacies. The current investigation sheds light on the potential hepatoprotective effect of SFN against VPA-induced liver injury in rats. Twice daily VPA (700 mg/kg, i.p.) for 7 days induced significant biochemical alterations and hepatic histopathological damage. SFN (0.5 mg/kg, orally) for 7 days significantly boosted liver function biomarkers; it reduced serum alanine transaminase, aspartate aminotransferase, and alkaline phosphatase, and restored serum albumin concentration in a significant manner. Meanwhile, SFN significantly mitigated VPA-induced histopathological alterations. To highlight the mechanisms implicated in the observed hepatoprotective action, hepatic malondialdehyde and tumour necrosis factor α content significantly declined with concomitant increase in hepatic heme oxygenase-1 content and glutathione concentration with SFN treatment. In conclusion, SFN can significantly ameliorate VPA-induced hepatotoxicity and liver injury primarily by direct association between antioxidant and anti-inflammatory properties.

Thiazolopyrimidines are well known to be designed to act as bio-isosteric analogues of purine nucleus. They proved to show a wide range of biological activities, such as anticancer, anti-inflammatory, antifungal, antiviral and antitubercular activity. In this study, a literature survey was thoroughly performed to elect the most active thiazolopyrimidine-containing scaffolds, acting as anticancer agents, to be subjected to extensive computational studies in order to explore the possible credible mode of their anticancer activity. First, drug-likeness was investigated for the most active derivatives, followed by molecular docking study against Cyclin-dependent kinases (CDK), Vascular endothelial growth factor receptor (VEGFR) and Phosphoinositide 3-kinases (PI3K) enzymes in order to assess their binding energy and propose the mode of action. Next, contact preference and surface mapping studies were carried out to explain the presence of remarkable affinity of certain analogues towards a specific enzyme, in addition to providing more information about their activity. Finally, physicochemical properties, Lipinski’s rule of five and ADMET prediction studies were applied to predict the best route of administration and to suggest the pharmacokinetics of the most promising candidates.

A new series of thiazolo[4,5-d]pyrimidine derivatives was rationally designed and synthesized as dual PI3K/CDK6 inhibitors to concurrently target key oncogenic pathways via isoform selectivity. Structural optimization at C5 and C7 positions was explored to enhance interactions within the PI3K ATP-binding site and CDK6 hinge region. The new compounds showed significant cytotoxicity against colorectal (HCT 116), lung (A549), hepatocellular (SNU-449), and breast (MCF7) cancer cell lines, with minimal effects on normal human lung fibroblasts (CCD-16Lu). Compound 8b demonstrated balanced low-micromolar potency across multiple cell lines with IC50 range of 5.94-31.73 μM, and superior overall efficacy compared to its analogue 5b. SAR analysis showed that p-methoxyphenyl substitution improved both potency and spectrum, whereas m-substitution enhanced HCT 116 selectivity. Enzymatic assays confirmed dual PI3K/CDK6 inhibition, supported by cell cycle arrest, apoptosis induction, and molecular docking studies. These findings identify 8b as a promising candidate for dual kinase-targeted anticancer therapy.