Novel substituted hydrazono indolo[2,1-b]quinazoline-6,12-dione analogues as cytostatic agents: Synthesis, crystal structure, biological evaluation and molecular docking studies

被引:20
作者
Guda, Ramu [1 ]
Narsimha, Sirassu [1 ]
Babu, Ramavath [2 ]
Muthadi, Srujana [3 ]
Lingabathula, Harikiran [3 ]
Palabindela, Rambabu [1 ]
Yellu, Narsimha Reddy [3 ]
Kumar, Girijesh [4 ]
Kasula, Mamatha [1 ]
机构
[1] Kakatiya Univ, Dept Chem, Warangal 506009, Andhra Pradesh, India
[2] Univ Hyderabad, Sch Chem, Hyderabad 500046, Andhra Pradesh, India
[3] Kakatiya Univ, Univ Coll Pharmaceut Sci, Warangal 506009, Andhra Pradesh, India
[4] Panjab Univ, Dept Chem, Chandigarh 160014, India
关键词
Tryptanthrin; Cytotoxicity; Antibacterial activity; Antifungal activity; Molecular docking; IDO1; TRYPTANTHRIN DERIVATIVES; BREAST-CANCER; INHIBITORS; CELLS; PROSTAGLANDIN; APOPTOSIS;
D O I
10.1016/j.bmcl.2016.10.006
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
A series of novel substituted hydrazono indolo[2,1-b]quinazoline-6,12-dione analogues have been synthesized and screened for their in vitro cytotoxic and antimicrobial activities. Among all the target compounds, 3c exhibited the most potent inhibitory activity against three cancer cell lines MCF-7, A549, HeLa with IC50 values 07.14 +/- 1.285 mu M, 09.18 +/- 0.968 mu M and 10.57 +/- 0.581 mu M respectively, while maintaining low toxicity towards non-cancer originated cell line, HEK-293. The detailed studies about molecular interactions with probable target protein indoleamine 2,3-dioxygenase (IDO1) were done by using docking simulations. The results from docking models are in consistent with the experimental in vitro cytotoxic activity conclusions i.e. 3c shows the highest binding energy -11.25 kcal/mol. Furthermore, antimicrobial studies revealed that the compound 3e has shown excellent anti bacterial activity against four tested strains and the compounds 3b, 3e and 3f have shown good anti fungal activity against two tested organisms as compared with their standard drugs. (C) 2016 Elsevier Ltd. All rights reserved.
引用
收藏
页码:5517 / 5523
页数:7
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