Formulation Development of Novel Curcumin Analogue Loaded Non-aqueous Gel and Curcumin Analogue Loaded Nanoparticle (CA-NP) Gel for Topical Use and In-vitro Antioxidant Study

In this paper we have reported development of suitable dosage form for novel curcumin analogue synthesized in our laboratory. The work involves preformulation studies of synthesized curcumin analogue followed by preparation and optimization of non-aqueous gel and curcumin loaded (CA-NP) nanoparticle gel. The formulated gels were observed visually for clarity, homogeneity, and phase separation. They were tested for their appearance and presence of any aggregates. Curcumin analogue loaded PLGA nanoparticles were prepared by using the nanoprecipitation -solvent evaporation method and further optimized. In-vitro antioxidant activity of formulation was then evaluated using DPPH radical scavenging activity. The gel exhibited good antioxidant activity with IC50 value of 5.39 μg/ml.

(E)-5-Benzyl-7-(3,4-dimethoxybenzylidene)-3-(3,4-dimethoxyphenyl)-2-phenyl-3,3a,4,5,6,7-hexahydro-2H-pyrazolo[4,3c] Pyridine

A new pyrazolo-pyridine analogue (title compound) was synthesized in two steps. The first stage was synthesis of monoketone curcumin analogue through Claisen–Schmidt reaction. The second stage was synthesis of the title compound through intermolecular cyclization under reflux condition. The structure of the title compound has been confirmed by spectroscopic analysis including UV, FT-IR, HRMS, 1D NMR (1H-NMR, 13C-NMR, 1D-TOCSY), and 2D NMR (COSY, HSQC, HMBC). Based on the DPPH assay, the compound has moderate antioxidant activity, with an IC50 value of 194.06 ± 7.88 µg/mL (0.337 mM).

Pentagamaboronon-0-Sorbitol Induces Apoptosis through Elevation of Reactive Oxygen Species in Triple Negative Breast Cancer Cells

Breast cancer is the most common type of cancer causing mortality for women due to metastasis. More than 50% of breast cancer patients are suffered lung metastases. One strategy to target the cancerous cell is Boron Neutron Captured Therapy (BNCT) which showed high affinity toward cancer cells and reported to have anti-proliferative as well as anti-metastatic activities. Pentagamaboronon-0 (PGB-0) is a curcumin analogue substance which had reported to exert anticancer activities against Her-2 expressing as well as triple negative breast cancer cells. Despite its great potency as BNCT agent candidate, this compound also exerted several anticancer properties. Complex formation of this substance with sorbitol was achieved to improve the solubility and maximize compound’s delivery to the target cells. This study aimed to investigate the ability of Pentagamaboronon-0-Sorbitol (PGB-0-So) to modulate cell cycle and induce apoptosis especially through the mechanisms of reactive oxygen species (ROS) modulation. The 3-(4,5-dimethylthiazzol-2yl)-2,5-diphenyltetrazolium (MTT) cytotoxicity assay of PGB-0-So against 4T1 breast cancer cell line were found to exert potential effect in dose-dependent manner with lethal concentration (IC50) values of 39 μM. The cytotoxicity of PGB-0-So complex was found to be increased considerably compared with that of PGB-0. Cell cycle modulation identified using propidium iodide (PI) staining showed cell accumulation in S phase following treatment with PGB-0-So. Apoptosis induction assay analyzed using flowcytometer with Annexin V and PI staining on its IC50 dose was found to induce programmed cell death (apoptosis). The sub-IC50 treatment of this compound was also improved the cellular ROS level which also took role in apoptosis induction. These findings suggest that PGB-0-So is potential as an anticancer agent.Keywords: Curcumin analogue, PGB-0-So, Anticancer, 4T1 cell line, ROS modulation.

Curcumin Analogue L48H37 Suppresses Human Osteosarcoma U2OS and MG-63 Cells’ Migration and Invasion in Culture by Inhibition of uPA via the JAK/STAT Signaling Pathway

Osteosarcoma, the most prevalent malignant bone tumor in the pediatric age group, is responsible for the great majority of cancer-associated deaths owing to its highly metastatic potential. The anti-metastatic effects of the new curcumin analogue L48H37 in human osteosarcoma are still unknown; hence, we investigated whether L48H37 represses human osteosarcoma cells’ biological behavior of migratory potential and invasive activities and attempted to delve into its underlying mechanisms. L48H37 up to 5 μM inhibited, without cytotoxicity, the motility, migration, and invasion of human osteosarcoma U2OS and MG-63 cells. In U2OS cells, the human protease array revealed an obvious decrease in urokinase plasminogen activator (uPA) expression after L48H37 treatment, and L48H37 actually reduced the level, protein and mRNA expression, and promoter activity of uPA dose-dependently. L48H37 decreased the phosphorylation of STAT3, JAK1, JAK2, and JAK3 in U2OS cells, but did not affect the phosphorylation of ERK, JNK, p38, and Akt. Using colivelin, an activator of STAT3, the L48H37-induced decrease in uPA and migratory potential could be countered as expected. Collectively, L48H37 represses the invasion and migration capabilities of U2OS and MG-63 cells by the suppression of uPA expression and the inhibition of JAK/STAT signaling. These results suggest that L48H37 may be a potential candidate for anti-metastatic treatment of human osteosarcoma.