Synthesis of Palladium-Catalysed C-C Bond Forming 5-Chloro Quinolines via Suzuki-Miyaura Coupling; Anti-Pancreatic Cancer Screening on PANC-1 Cell Lines.

Pancreatic cancer is the most severe among other cancers due to its late detection and less chance of survivability. Heterocycles are proven ring systems in the treatment of various cancers and this is due to the presence of two biodynamic molecules combined, which have a greater synergistic efficacy in many anticancer drugs. Quinoline and pyridine ring systems are brought together to obtain greater potency and this is achieved by coupling both using Pd-catalyst, and in the present investigation, Suzuki-Miyaura coupling (SMC) reactions are adopted to generate potent molecular entities. Pancreatic cancer is difficult to treat due to overexpression of the VEGFR2 protein. VEGFR2 is targeted to design the molecules of quinoline-coupled pyridine moieties and is docked to evaluate the protein-ligand interaction at the binding site. The binding affinity of conjugates revealed the potency and capability of ligands to inhibit the VEGFR2 pathway. The in-silico ADMET properties determined their inherent pharmacokinetic feasibility. The synthesized conjugates have been evaluated by MTT assay against the human pancreatic cancer cell lines (PANC-1). Among the series, compounds 5d, 5e, and 5h exhibited a greater inhibitory activity against the cell lines with an IC50 value of 82.32±1.38, 54.74±1.18 and 80.35±1.68 µM. In the present exploration, 5e exhibited greater inhibitory activity and it could be a promising lead for the development of new chemotherapeutics against pancreatic cancer.

Antiproliferative Effects of Artabotrys odoratissimus Fruit Extract and its Bioactive Fraction through Upregulation of p53/γH2AX Signals and G2/M Phase Arrest in MIA PaCa-2 Cells.

BACKGROUND: Artabotrys odoratissimus (Annonaceae) is a medicinal and ornamental plant widely cultivated in Southeast Asia for its famous ylang ylang essential oil. The fruits of this plant are used for health benefits, but very little is studied about the bioactive principles, their role in regulating oxidative stress and tumour progression. OBJECTIVE: The study aimed to evaluate the antiproliferative effects of fruit extract of Artabotrys odoratissimus and its bioactive fraction using cell-based assays. METHODS: The free radical scavenging and antiproliferative effects of Artabotrys odoratissimus fruit ethyl acetate (FEA) extract and its bioactive fraction were evaluated using cell viability assays, colony formation assay, double staining assay, reactive oxygen species (ROS) assay, comet assay, cell cycle analysis, and western blotting. RESULTS: The extract showed phenolic content of 149.8±0.11µg/mg Gallic acid equivalents and flavonoid content of 214.47±4.18 µg/mg Quercetin. FEA showed an IC50 value of 76.35 µg/ml in the ABTS assay and an IC50 value of 134.3±7.8 µg/ml on MIA PaCa-2 cells. The cells treated with 125 µg/ml and 250 µg/ml FEA showed increased apoptotic cells in Double staining assay, DNA damage during comet assay, enhanced ROS, and cell cycle arrest at G2M phase at 125 µg/ml and 250 µg/ml. The active fraction AF5 showed an IC50 value of 67±1.26 µg/ml on MIA PaCa-2 cells during MTT assay, displayed potential antiproliferative effects, and showed a marked increase in the expression of γH2AX and p53. CONCLUSION: These results prove that the fruit extract and the bioactive fraction demonstrate oxidative stress-mediated DNA damage, leading to apoptosis in the MIA PaCa-2 cell line.