Design, synthesis and biological evaluation of new quinoline derivatives as potential antitumor agents
| Autor: | Qiuhua Huang, Liqin Qiu, Tong Su, Hui-Hui Zhang, Run-Lei Du, Xiao-Dong Zhang, Jiongchang Zhu, Rihui Cao, Rongqin Sun |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Colorectal cancer ATG5 Antineoplastic Agents Apoptosis Pharmacology 01 natural sciences Autophagy-Related Protein 5 HeLa 03 medical and health sciences chemistry.chemical_compound Structure-Activity Relationship Cell Line Tumor Drug Discovery medicine Autophagy Animals Humans IC50 030304 developmental biology Cell Proliferation 0303 health sciences Mice Inbred BALB C biology Molecular Structure 010405 organic chemistry Chemistry Organic Chemistry Quinoline General Medicine biology.organism_classification medicine.disease Xenograft Model Antitumor Assays 0104 chemical sciences Mechanism of action Cell culture Drug Design Quinolines medicine.symptom Drug Screening Assays Antitumor Colorectal Neoplasms |
| Zdroj: | European journal of medicinal chemistry. 178 |
| ISSN: | 1768-3254 |
| Popis: | A series of new quinoline derivatives was designed, synthesized and evaluated for their antiproliferative activity. The results demonstrated that compounds 11p, 11s, 11v, 11x and 11y exhibited potent antiproliferative activity with IC50 value of lower than 10 μM against seven human tumor cell lines, and N-(3-methoxyphenyl)-7- (3-phenylpropoxy)quinolin-4-amine 11x was found to be the most potent antiproliferative agent against HCT-116, RKO, A2780 and Hela cell lines with an IC50 value of 2.56, 3.67, 3.46 and 2.71 μM, respectively. The antitumor efficacy of the representative compound 11x in mice was also evaluated, and the results showed that compound 11x effectively inhibited tumor growth and decreased tumor weight in animal models. Further investigation on mechanism of action indicated that compound 11x could inhibit colorectal cancer growth through ATG5-depenent autophagy pathway. Therefore, these quinoline derivatives are a new class of molecules that have the potential to be developed as new antitumor drugs. |
| Databáze: | OpenAIRE |
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