Novel Isoquinolinamine and Isoindoloquinazolinone Compounds Exhibit Antiproliferative Activity in Acute Lymphoblastic Leukemia Cells

Roolf, Catrin; Saleweski, Jan-Niklas; Stein, Arno; Richter, Anna; Maletzki, Claudia; Sekora, Anett; Escobar, Hugo Murua; Wu, Xiao-Feng; Beller, Matthias; Junghanss, Christian

추천

검색

자료유형: 학술저널

저자정보: Roolf, Catrin (Department of Medicine, Clinic III - Hematology, Oncology, Palliative Medicine, Rostock University Medical Center) Saleweski, Jan-Niklas (Department of Medicine, Clinic III - Hematology, Oncology, Palliative Medicine, Rostock University Medical Center) Stein, Arno (Department of Medicine, Clinic III - Hematology, Oncology, Palliative Medicine, Rostock University Medical Center) Richter, Anna (Department of Medicine, Clinic III - Hematology, Oncology, Palliative Medicine, Rostock University Medical Center) Maletzki, Claudia (Department of Medicine, Clinic III - Hematology, Oncology, Palliative Medicine, Rostock University Medical Center) Sekora, Anett (Department of Medicine, Clinic III - Hematology, Oncology, Palliative Medicine, Rostock University Medical Center) Escobar, Hugo Murua (Department of Medicine, Clinic III - Hematology, Oncology, Palliative Medicine, Rostock University Medical Center) Wu, Xiao-Feng (Leibniz-Institute for Catalysis at the University of Rostock) Beller, Matthias (Leibniz-Institute for Catalysis at the University of Rostock) Junghanss, Christian (Department of Medicine, Clinic III - Hematology, Oncology, Pal)

저널정보: 한국응용약물학회 Biomolecules & Therapeutics(구 응용약물학회지) Biomolecules & therapeutics 제27권 제5호

발행연도: 2019.1

수록면: 492 - 501 (10page)

이용수

📌

연구주제

📖

연구배경

🔬

연구방법

🏆

연구결과

초록· 키워드

오류제보하기

Nitrogen-containing heterocycles such as quinoline, quinazolinones and indole are scaffolds of natural products and have broad biological effects. During the last years those structures have been intensively synthesized and modified to yield new synthetic molecules that can specifically inhibit the activity of dysregulated protein kinases in cancer cells. Herein, a series of newly synthesized isoquinolinamine (FX-1 to 8) and isoindoloquinazolinone (FX-9, FX-42, FX-43) compounds were evaluated in regards to their anti-leukemic potential on human B- and T- acute lymphoblastic leukemia (ALL) cells. Several biological effects were observed. B-ALL cells (SEM, RS4;11) were more sensitive against isoquinolinamine compounds than T-ALL cells (Jurkat, CEM). In SEM cells, metabolic activity decreased with $10{\mu}M$ up to 26.7% (FX-3), 25.2% (FX-7) and 14.5% (FX-8). The 3-(p-Tolyl) isoquinolin-1-amine FX-9 was the most effective agent against B- and T-ALL cells with IC50 values ranging from 0.54 to $1.94{\mu}M$. None of the tested compounds displayed hemolysis on erythrocytes or cytotoxicity against healthy leukocytes. Anti-proliferative effect of FX-9 was associated with changes in cell morphology and apoptosis induction. Further, influence of FX-9 on PI3K/AKT, MAPK and JAK/STAT signaling was detected but was heterogeneous. Functional inhibition testing of 58 kinases revealed no specific inhibitory activity among cancer-related kinases. In conclusion, FX-9 displays significant antileukemic activity in B- and T-ALL cells and should be further evaluated in regards to the mechanisms of action. Further compounds of the current series might serve as templates for the design of new compounds and as basic structures for modification approaches.

#Acute lymphoblastic leukemia #Heterocycles #Isoquinolinamine #Isoindoloquinazolinone #Apoptosis #Kinase inhibitor

참고문헌 (48)

참고문헌 신청

Akhtar, M. J / 2017 / Recent advances in the synthesis and anticancer activity of some molecules other than nitrogen containing heterocyclic moeities / Mini Rev. Med. Chem 17:1602~1632

Ardito, F / 2017 / The crucial role of protein phosphorylation in cell signaling and its use as targeted therapy(review) / Int. J. Mol. Med 40:271~280

Buontempo, F / 2014 / Cytotoxic activity of the casein kinase 2 inhibitor CX-4945 against T-cell acute lymphoblastic leukemia : targeting the unfolded protein response signaling / Leukemia 28:543~553

Buontempo, F / 2017 / Therapeutic targeting of CK2 in acute and chronic leukemias / Leukemia 32:1~10

Cani, A / 2015 / Triple Akt inhibition as a new therapeutic strategy in T-cell acute lymphoblastic leukemia / Oncotarget 6:6597~6610

함께 읽어보면 좋을 논문

논문 유사도에 따라 DBpia 가 추천하는 논문입니다. 함께 보면 좋을 연관 논문을 확인해보세요!