Anti-proliferative Activity of 3,5-Diaminoindazole Analogues
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Cancer is the second leading cause of death worldwide. Small-molecule anticancer agents with tolerable safety profiles have been developed to improve survival rates. Indazole analogues have received considerable attention due to their anticancer properties. A series of N3-acyl-N5-pyrimidinyl-3,5-diaminoindazoles were synthesized and their antiproliferative activities were evaluated in Caki, A549, HepG2, AMC-HN4, and SNU484 human cancer cell lines. Cellular selectivity of 3,5-diaminoindazole with a modified structure of the N5-pyrimidinyl substituent was studied. While both compounds 9a and 9b showed a high selectivity for the HepG2 cell line, compound 9b had a higher selectivity than 9a, with an IC50«0.1 μM.
Abstract
Cancer is the second leading cause of death worldwide. Small-molecule anticancer agents with tolerable safety profiles have been developed to improve survival rates. Indazole analogues have received considerable attention due to their anticancer properties. A series of N3-acyl-N5-pyrimidinyl-3,5-diaminoindazoles were synthesized and their antiproliferative activities were evaluated in Caki, A549, HepG2, AMC-HN4, and SNU484 human cancer cell lines. Cellular selectivity of 3,5-diaminoindazole with a modified structure of the N5-pyrimidinyl substituent was studied. While both compounds 9a and 9b showed a high selectivity for the HepG2 cell line, compound 9b had a higher selectivity than 9a, with an IC50«0.1 μM.
참고문헌 (22)
- Jemal A, "Global cancer statistics", CA: A Cancer J Clin, 61, pp.69~90 (2011)
- Valler MJ, "Diversity screening versus focussed screening in drug discovery", Drug Discov Today, 5, pp.286~293 (2000)
- Coussens NP, "Small-Molecule Screens: A Gateway to Cancer Therapeutic Agents with Case Studies of Food and Drug Administration-Approved Drugs", Pharmacol Rev, 69, pp.479~496 (2017)
- Li W, "Cell-based assays for profiling activity and safety properties of cancer drugs", J Pharmacol Toxicol Methods, 54, pp.313~319 (2006)
- Mateus A, "Prediction of intracellular exposure bridges the gap between target- and cell-based drug discovery", Proc Natl Acad Sci U S A, 114, pp.E6231~E6239 (2017)
- Linciano P, "Exploiting the 2-Amino-1,3,4-thiadiazole Scaffold To Inhibit Trypanosoma brucei Pteridine Reductase in Support of Early-Stage Drug Discovery", ACS Omega, 2, pp.5666~5683 (2017)
- Li Y-J, "Synthesis, biological evaluation and molecular modeling of 1,3,4-thiadiazol-2-amide derivatives as novel antitubulin agents", Biorg Med Chem, 22, pp.4312~4322 (2014)
- Naim MJ, "Therapeutic journey of 2,4-thiazolidinediones as a versatile scaffold: An insight into structure activity relationship", Eur J Med Chem, 129, pp.218~250 (2017)
- Herberich B, "Discovery of Highly Selective and Potent p38Inhibitors Based on a Phthalazine Scaffold", J Med Chem, 51, pp.6271~6279 (2008)
- 강지희, "Synthesis of (Z)-3-((1H-imidazol-5-yl)methylene)indolin-2-one Derivatives as Pim Kinase Inhibitors", Quantitative Bio-Science, 37(1), pp.33~42 (2018), 자연과학연구소[DOI]
- Ah Yeon Lee, "1,3,4-Oxadiazole-2(3H)-thione as a New Scaffold for Pim Kinase Inhibitors", Quantitative Bio-Science, 37(2), pp.113~124 (2018), 자연과학연구소[DOI]
- Dadashpour S, "Indole in the target-based design of anticancer agents: A versatile scaffold with diverse mechanisms", Eur J Med Chem, 150, pp.9~29 (2018)
- Dong J, "Recent Advances in the Development of Indazole-based Anticancer Agents", ChemMedChem, 13, pp.1490~1507 (2018)
- Trott O, "AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading", J Comput Chem, 31, pp.455~461 (2010)
- Lee J, "Synthesis and biological evaluation of 3,5-diaminoindazoles as cyclin-dependent kinase inhibitors", Bioorg Med Chem Lett, 18 (2008)
- Lee J, "Synthesis and anti-proliferative activity evaluation of N 3-acyl-N 5-aryl-3, 5-diaminoindazole analogues as anti-head and neck cancer agent", Daru, 22, pp.4~ (2014)
- pyridines: potent inhibitors of glycogen synthase kinase-3 (GSK-3), "Bioorg Med Chem Lett", 2003, 3055~3057
- pyridines: potent and selective inhibitors of glycogen synthase kinase-3 (GSK-3), "Bioorg Med Chem Lett", 2003, 3059~3062
- Taha MO, "Pharmacophore Modeling, Quantitative Structure-Activity Relationship Analysis, and in Silico Screening Reveal Potent Glycogen Synthase Kinase-3βInhibitory Activities for Cimetidine, Hydroxychloroquine, and Gemifloxacin", J Med Chem, 51, pp.2062~2077 (2008)
- ine derivatives as GSK-3 inhibitors: CoMFA and molecular docking studies, "Eur J Med Chem", 2008, 949~957
- Tahir Ali C, "Cyclin-Dependent Kinase-2 as a Target for Cancer Therapy: Progress in the Development of CDK2 Inhibitors as Anti-Cancer Agents", Curr Med Chem, 22, pp.237~263 (2015)
- Igea A, "The Stress Kinase p38α as a Target for Cancer Therapy", Cancer Res, 75, pp.3997~4002 (2015)