sirolimus has been researched along with quinoline* in 2 studies
2 other study(ies) available for sirolimus and quinoline
| Article | Year |
|---|---|
Mechanistic investigation of synergistic interaction of tocopherol succinate with a quinoline-based inhibitor of mammalian target of rapamycin.
Cancer monotherapy is associated with various limitations; therefore, combination chemotherapy is widely explored for optimum drug efficacy. In this study, 4-(N-Phenyl-N'-substituted benzenesulfonyl)-6-(4-hydroxyphenyl) quinoline-based mammalian target of rapamycin (mTOR) inhibitor (IIIM-4Q) was investigated in combination with tocopherol succinate (TOS), and the mechanism of cytotoxicity was elucidated.. The cytotoxic potential of IIIM-4Q and TOS was evaluated in five cell lines. Further, to understand the mechanism of cytotoxicity of IIIM-4Q, TOS and their combination, various studies including morphological analysis using scanning electron microscopy and 6-diamidino-2-phenylindole (DAPI) staining, estimation of reactive oxygen species (ROS) level, measurement of mitochondrial membrane potential (MMP), in-vitro cell migration assay, Western blotting and staining with acridine orange (AO) for autophagy detection were performed.. Investigated combination was synergistic in nature and exhibited greater oxidative stress and mitochondrial dysfunction in pancreatic cancer cells. The migration potential of MIA PaCa-2 cells was significantly mitigated under the influence of this combination, and morphological changes such as chromatin condensation and nuclear blebbing were observed. Also, poly (adenosine diphosphate-ribose) polymerase cleavage and caspase-3 activation were observed in IIIM-4Q and TOS combination-treated cells.. The investigated combination synergistically inhibited proliferation of MIA PaCa-2 cells through simultaneous induction of autophagy followed by apoptosis, and this combination demonstrated potential for further translational studies. Topics: alpha-Tocopherol; Apoptosis; Autophagy; Cell Line, Tumor; Poly(ADP-ribose) Polymerases; Quinolines; Sirolimus; TOR Serine-Threonine Kinases | 2022 |
Discovery of novel quinoline-based mTOR inhibitors via introducing intra-molecular hydrogen bonding scaffold (iMHBS): The design, synthesis and biological evaluation.
A series of quinoline derivatives featuring the novelty of introducing intra-molecular hydrogen bonding scaffold (iMHBS) were designed, synthesized and biologically evaluated for their mTOR inhibitory activity, as well as anti-proliferative efficacies against HCT-116, PC-3 and MCF-7 cell lines. As a result, six compounds exhibited significant inhibition against mTOR with IC50 values below 35nM. Compound 15a, the most potent mTOR inhibitor reported herein (IC50=14nM), also displayed the most favorable cellular activities, with the IC50 values of 0.46, 0.61 and 0.24μM against HCT-116, PC-3 and MCF-7, respectively. Besides, several compounds in this series were identified to be selective over class I PI3Ks. Further western blot analysis of 16b, a representative compound in this series, highlighted their advantage in surmounting the S6K/IRS1/PI3K negative feedback loop upon dual inhibition of mTORC1 and mTORC2. In addition to the remarkable activity, 15a demonstrated acceptable stability in simulated gastric fluid (SGF), simulated intestinal fluid (SIF) and liver microsome, thereby being valuable for extensive in vivo investigation. Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Drug Design; HCT116 Cells; Humans; Hydrogen Bonding; MCF-7 Cells; Mechanistic Target of Rapamycin Complex 1; Mechanistic Target of Rapamycin Complex 2; Molecular Docking Simulation; Multiprotein Complexes; Neoplasms; Phosphatidylinositol 3-Kinases; Protein Kinase Inhibitors; Quinolines; Signal Transduction; TOR Serine-Threonine Kinases | 2015 |