ABSTRACT
A series of 1,2,3-triazole coronopilin congeners have been designed and synthesized by employing click chemistry approach starting from parthenin and evaluated for their cytotoxicity against a panel of six human cancer cell lines (PC-3, THP-1, HCT-15, HeLa, A-549 and MCF-7). While many compounds exhibited significant anticancer activity, compound 3a, was found to be the most promising analogue in this series with IC50 values of 3.1 µM on PC-3 cell line. Flow-cytometric studies showed that 1,2,3-triazole derivative-3a induce dose dependent apoptosis in the sub G1 phase. This lead molecule-3a was further studied for NF-κB (p65) transcription factor inhibitory activity using Elisa and western blotting analysis which confirmed concentration dependent inhibitory activity against NF-κB, p65 with 80% inhibition in 24 h at 100 µM.
Subject(s)
Antineoplastic Agents/pharmacology , Azulenes/pharmacology , Drug Design , Sesquiterpenes/pharmacology , Triazoles/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Azulenes/chemical synthesis , Azulenes/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , HeLa Cells , Humans , MCF-7 Cells , Molecular Structure , Sesquiterpenes/chemical synthesis , Sesquiterpenes/chemistry , Structure-Activity Relationship , Triazoles/chemical synthesis , Triazoles/chemistryABSTRACT
Polymer-based nanotechnologies are proposed to be an alternative for drug administration, delivery and targeting to those of conventional formulations. The blood brain barrier is frequently a rate-limiting factor in determining permeation of a drug into brain. In this study, the surface-engineered long-circulating PLGA nanoparticles (NPs) were assessed for brain-specific delivery. Long circulating NPs of PLGA- and PEG-synthesised copolymer were prepared by emulsification solvent evaporation method. Further, the surface of PEGylated NPs was modified by anchoring transferrin (Tf) ligand for receptor-mediated targeting to brain. NPs were characterised for shape and size, zeta potential, entrapment efficiency and in vitro drug release. In vitro cytotoxicity studies were performed on human cancer cell lines. Confocal Laser Scanning Microscopy studies show the enhanced uptake of Tf-appended PEGylated NPs and their localisation in the brain tissues. Hence, the specific role of Tf ligand on PEGylated NPs for brain delivery was confirmed.
