Development of novel thiazolidine-2,4-dione derivatives as PPAR-γ agonists through design, synthesis, computational docking, MD simulation, and comprehensive in vitro and in vivo evaluation.

The present study was conducted to develop new novel 2,4-thiazolidinedione derivatives (3h-3j) as peroxisome proliferator-activated receptor-γ (PPAR-γ) modulators for antidiabetic activity. The objective was to overcome the adverse effects of existing thiazolidinediones while maintaining their pharmacological benefits. The synthesized compounds were elucidated based on FT-IR, 1H-NMR, 13C-NMR, and MS techniques. Molecular docking was utilized to investigate the interaction binding modes, binding free energy, and amino acids engaged in the compounds' interactions with the target protein. Subsequently, molecular dynamics modelling was used to assess the stability of the top-docked complexes and an assay was utilized to assess the cytotoxicity of the compounds to C2C12 myoblasts. Compounds 3h-3j exhibited PPAR-γ modulatory activity and demonstrated significant hypoglycaemic effects when compared to the reference drug pioglitazone. The new compounds were evaluated for their in vivo blood glucose-lowering potential by using a dexamethasone-induced diabetic rat model. All the compounds showed a hypoglycaemic effect of 108.04 ± 4.39, 112.55 ± 6.10, and 117.48 ± 43.93, respectively, along with pioglitazone (153.93 ± 4.61) compared to the diabetic control. Additionally, all the compounds significantly reduced AST and ALT levels and did not cause liver damage.

Cytotoxic and apoptotic efficacy of Alkanna tinctoria on glioma cells.

Glioblastoma is the most common lethal form of malignant tumor that arises from the central nervous system. The present-day therapeutic strategies possess their own pros and cons. Hence, there is a need to look back into the traditional medicines that could be potential agents to treat glioblastoma. One of the potential approaches in anticancer therapy is to induce tumor cell death by natural phytochemicals which pose minimum adverse effects. In this study, we aimed to evaluate the cytotoxic and apoptotic effects of hexane extract of Alkanna tinctoria (L.) Tausch on U87MG cells using various biological activities. The results obtained from our study state that the plant extract showed potential anticancer activity against U87MG cells. The molecular docking studies indicated that alkannin and shikonin present in the extract could efficiently bind to brain tumor cell receptors and showed better docking scores when compared to commercially available drugs temozolomide and bevacizumab.

In vitro blood brain barrier models: Molecular aspects and therapeutic strategies in glioma management.

Glioma management is the most challenging task in clinical oncology due to numerous reasons. One of the major hurdles in glioma therapy is the presence of blood brain barrier which resists the entry of most of the drugs into the brain. However, in case of tumors, blood brain barrier integrity is compromised, which in turn can be advantageous in delivering the drugs, if the therapeutic module is strategically modified. For such improvised therapeutic strategy, it is necessary to understand the molecular composition and profiling of blood brain barrier and blood brain tumor barrier. This review mainly focuses on the composition, markers expressed on the blood brain barrier which will help the readers to understand its basic environment. It also gives a detailed account of the various in vitro models that are used to study the nature of the blood brain barrier and describes various strategies in improvising the drug delivery in glioma management.

Combining Angiogenesis Inhibitors with Radiation: Advances and Challenges in Cancer Treatment.

BACKGROUND: Radiation therapy is a widely employed modality that is used to destroy cancer cells, but it also tends to induce changes in the tumor microenvironment and promote angiogenesis. Radiation, when used as a sole means of therapeutic approach to treat cancer, tends to trigger the angiogenic pathways, leading to the upregulation of several angiogenic growth factors such as VEGF, bFGF, PDGF and angiogenin. This uncontrolled angiogenesis leads to certain angiogenic disorders like vascular outgrowth and an increase in tumor progression that can pose a serious threat to patients. OBJECTIVE: This review emphasizes on various components of the tumor microenvironment, angiogenic growth factors and biological effects of radiation on tumors in provoking the relapse. It also describes the angiogenic mechanisms that trigger the tumor relapse after radiation therapy and how angiogenesis inhibitors can help in overcoming this phenomenon. It gives an overview of various angiogenesis inhibitors in pre-clinical as well as in clinical trials. CONCLUSION: The review focuses on the beneficial effects of the combinatorial therapeutic approach of anti-angiogenesis therapy and radiation in tumor management.