124673-89-8Relevant academic research and scientific papers
Improving the Potency of Cancer Immunotherapy by Dual Targeting of IDO1 and DNA
Fang, Kun,Dong, Guoqiang,Wang, Hongyu,He, Shipeng,Wu, Shanchao,Wang, Wei,Sheng, Chunquan
, p. 30 - 36 (2018)
Herein we report the first exploration of a dual-targeting drug design strategy to improve the efficacy of small-molecule cancer immunotherapy. New hybrids of indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors and DNA alkylating nitrogen mustards that respectively target IDO1 and DNA were rationally designed. As the first-in-class examples of such molecules, they were found to exhibit significantly enhanced anticancer activity in vitro and in vivo with low toxicity. This proof-of-concept study has established a critical step toward the development of a novel and effective immunotherapy for the treatment of cancers.
Design, synthesis and biological evaluation of novel sesquiterpene mustards as potential anticancer agents
Xu, Yuan-Zhen,Gu, Xue-Yan,Peng, Shou-Jiao,Fang, Jian-Guo,Zhang, Ying-Mei,Huang, De-Jun,Chen, Jian-Jun,Gao, Kun
, p. 284 - 297 (2015/03/30)
Several novel series of sesquiterpene mustards (SMs) bearing nitrogen mustard and glutathione (GSH)-reactive α-methylene-γ-butyrolactone groups were successfully prepared for the first time and showed excellent antiproliferative activities in vitro. Among them, compounds 2e and 2g displayed the highest antiproliferative properties with IC50 values ranging from 2.5 to 8.7 μM. The selectivity of these two compounds was evaluated by SRB method against human cancer and normal hepatic cells (HepG2 and L02). The induction of apoptosis and effects on the cell cycle distribution with compounds 2e and 2g were investigated by Hoechst 33,258 staining and flow cytometry, which exhibited that they could induce selective cell apoptosis and cell cycle arrest in HepG2 and L02 cells. In addition, further investigation showed that compounds 2e and 2g could obviously inhibit the proliferation of HepG2 cells by inducing significant DNA cross-linking and depleting GSH in cell media. The good cytotoxicity and selectivity of compounds 2e and 2g pointed them as promising leads for anticancer drug design.
Synthesis and biological evaluation of new cytotoxic indazolo[4,3-gh] isoquinolinone derivatives
Shahabi, Manochehr,Schirmer, Eva,Shanab, Karem,Leepasert, Theerachart,Ruzicka, Jana,Holzer, Wolfgang,Spreitzer, Helmut,Aicher, Babette,Schmidt, Peter,Blumenstein, Lars,Müller, Gilbert,Günther, Eckhard
, p. 1846 - 1852 (2013/04/10)
A series of indazolo[4,3-gh]isoquinolinones derivatives have been synthesized to decrease cardiotoxic side effects in comparison to Mitoxantrone. The antiproliferative effects of different side chains were investigated and tested on at least four different cell lines of cervix, ovarian, CNS, NSCLC (non-small-cell lung cancer) and colon carcinoma. In addition to antiproliferative activities, influence on cell cycle and intercalation behavior have been tested.
