Design, synthesis, α-amylase and glucose diffusion inhibition, and molecular docking studies of new indenopyrazolones bearing benzothiazole derivatives.

An eco-friendly facile synthesis of a series of twenty 1-(4/6-substitutedbenzo[d]thiazol-2-yl)-3-(phenyl/substitutedphenyl)indeno[1,2-c]pyrazol-4(1H)-ones 7a-t was achieved by the reaction of 2-(benzoyl/substitutedbenzoyl)-(1H)-indene-1,3(2H)-dione 3a-t and 2-hydrazinyl-4/6-substitutedbenzo[d]thiazole 6a-t in presence of freshly dried ethanol and glacial acetic acid under reflux conditions in good yields. The newly synthesized derivatives were well characterized using different physical and spectral techniques (FTIR, 1H NMR & 13C NMR, and HRMS). All the compounds were subjected to assess their in vitro α-amylase and glucose diffusion inhibitory activity. Amongst them, the compounds 7i and 7l showed better α-amylase inhibitory activity demonstrating IC50 values of 92.99±1.94 µg/mL and 95.41±3.92 µg/mL, respectively in comparison to the standard drug acarbose (IC50 value of 103.60±2.15 µg/mL). The derivatives 7d and 7k exhibited good glucose diffusion inhibition with values of 2.25±1.16 µg/mL and 2.63±1.45 µg/mL, respectively with standard reference acarbose (2.76±0.55 µg/mL). The observed α-amylase inhibitory activity findings were corroborated through molecular docking investigations, particularly for the highly active compounds 7i (binding energy -8.0 kcal/mol) and 7l (binding energy -8.2 kcal/mol) respectively, in comparison to acarbose with a value of binding energy -6.9 kcal/mol for α-amylase.

Enhancing cancer immunotherapy: Exploring strategies to target the PD-1/PD-L1 axis and analyzing the associated patent, regulatory, and clinical trial landscape.

Cancer treatment modalities and their progression is guided by the specifics of cancer, including its type and site of localization. Surgery, radiation, and chemotherapy are the most often used conventional treatments. Conversely, emerging treatment techniques include immunotherapy, hormone therapy, anti-angiogenic therapy, dendritic cell-based immunotherapy, and stem cell therapy. Immune checkpoint inhibitors' anticancer properties have drawn considerable attention in recent studies in the cancer research domain. Programmed Cell Death Protein-1 (PD-1) and its ligand (PD-L1) checkpoint pathway are key regulators of the interactions between activated T-cells and cancer cells, protecting the latter from immune destruction. When the ligand PD-L1 attaches to the receptor PD-1, T-cells are prevented from destroying cells that contain PD-L1, including cancer cells. The PD-1/PD-L1 checkpoint inhibitors block them, boosting the immune response and strengthening the body's defenses against tumors. Recent years have seen incredible progress and tremendous advancement in developing anticancer therapies using PD-1/PD-L1 targeting antibodies. While immune-related adverse effects and low response rates significantly limit these therapies, there is a need for research on methods that raise their efficacy and lower their toxicity. This review discusses various recent innovative nanomedicine strategies such as PLGA nanoparticles, carbon nanotubes and drug loaded liposomes to treat cancer targeting PD-1/PD-L1 axis. The biological implications of PD-1/PD-L1 in cancer treatment and the fundamentals of nanotechnology, focusing on the novel strategies used in nanomedicine, are widely discussed along with the corresponding guidelines, clinical trial status, and the patent landscape of such formulations.