- Design and synthesis of a new class of 4-aminoquinolinyl- and 9-anilinoacridinyl schiff base hydrazones as potent antimalarial agents
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A series of novel 4-aminoquinolinyl and 9-anilinoacridinyl Schiff base hydrazones have been synthesized and evaluated for their antimalarial activity. All compounds were evaluated in vitro for their antimalarial activity against chloroquine-sensitive strain 3D7 and the chloroquine-resistant K1 strain of Plasmodium falciparum and for cytotoxicity toward Vero cells. Compounds 17, 20, and 21 displayed good activity against the 3D7 strain with IC50 values ranging from 19.69 to 25.38 nm. Moreover, compounds 16, 17, 21, 24, 32, and 33 exhibited excellent activities (21.64-54.26 nm) against K1 strain and several compounds displayed β-hematin inhibitory activity, suggesting that they act on the heme crystallization process such as CQ. Compounds were also found to be non-toxic with good selectivity index.
- Sharma, Moni,Chauhan, Kuldeep,Srivastava, Rajeev K.,Singh, Shiv V.,Srivastava, Kumkum,Saxena, Jitendra K.,Puri, Sunil K.,Chauhan, Prem M.S.
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p. 175 - 181
(2014/07/22)
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- Exploration of acridine scaffold as a potentially interesting scaffold for discovering novel multi-target VEGFR-2 and Src kinase inhibitors
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VEGFR-2 and Src kinases both play important roles in cancers. In certain cancers, Src works synergistically with VEGFR-2 to promote its activation. Development of multi-target drugs against VEGFR-2 and Src is of therapeutic advantage against these cancers. By using molecular docking and SVM virtual screening methods and based on subsequent synthesis and bioassay studies, we identified 9-aminoacridine derivatives with an acridine scaffold as potentially interesting novel dual VEGFR-2 and Src inhibitors. The acridine scaffold has been historically used for deriving topoisomerase inhibitors, but has not been found in existing VEGFR-2 inhibitors and Src inhibitors. A series of 21 acridine derivatives were synthesized and evaluated for their antiproliferative activities against K562, HepG-2, and MCF-7 cells. Some of these compounds showed better activities against K562 cells in vitro than imatinib. The structure-activity relationships (SAR) of these compounds were analyzed. One of the compounds (7r) showed low μM activity against K562 and HepG-2 cancer cell-lines, and inhibited VEGFR-2 and Src at inhibition rates of 44% and 8% at 50 μM, respectively, without inhibition of topoisomerase. Moreover, 10 μM compound 7r could reduce the levels of activated ERK1/2 in a time dependant manner, a downstream effector of both VEGFR-2 and Src. Our study suggested that acridine scaffold is a potentially interesting scaffold for developing novel multi-target kinase inhibitors such as VEGFR-2 and Src dual inhibitors.
- Luan, Xudong,Gao, Chunmei,Zhang, Nannan,Chen, Yuzong,Sun, Qinsheng,Tan, Chunyan,Liu, Hongxia,Jin, Yibao,Jiang, Yuyang
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experimental part
p. 3312 - 3319
(2011/07/08)
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- Synthesis of 9-anilinoacridine triazines as new class of hybrid antimalarial agents
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There is challenge and urgency to synthesize cost-effective chemotherapeutic agents for treatment of malaria after the widespread development of resistance to CQ. In the present study, we synthesized a new series of hybrid 9-anilinoacridine triazines usin
- Kumar, Ashok,Srivastava, Kumkum,Raja Kumar,Puri,Chauhan, Prem M.S.
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scheme or table
p. 6996 - 6999
(2010/06/16)
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