Design, synthesis and anticancer activity of 2-arylimidazo [1,2-a] pyridinyl-3-amines

被引：22

作者：

Yadav, Umesh Prasad ^{[1
,5
]}

Ansari, Arshad J. ^{[2
]}

Arora, Sahil ^{[3
]}

Joshi, Gaurav ^{[3
]}

Singh, Tashvinder ^{[1
]}

Kaur, Harsimrat ^{[1
]}

Dogra, Nilambra ^{[4
]}

Kumar, Raj ^{[3
]}

Kumar, Santosh ^{[5
]}

Sawant, Devesh M. ^{[2
]}

Singh, Sandeep ^{[1
]}

机构：

[1] Cent Univ Punjab, Dept Human Genet & Mol Med, Sch Hlth Sci, Bathinda 151401, India

[2] Cent Univ Rajasthan, Sch Chem Sci & Pharm, Dept Pharm, Ajmer 305817, India

[3] Cent Univ Punjab, Sch Pharmaceut Sci, Dept Pharmaceut Sci & Nat Prod, Bathinda 151401, India

[4] Panjab Univ, Ctr Syst Biol & Bioinformat, Chandigarh 160014, India

[5] All India Inst Med Sci, Dept Biochem, Patna, Bihar, India

来源：

BIOORGANIC CHEMISTRY | 2022年 / 118卷

关键词：

2-Arylimidazo[1; 2-a; pyridinyl-3-amines; Topoisomerase inhibitors; Anticancer; Western blotting; p53; TOPOISOMERASE-II-ALPHA; SOLVENT-FREE SYNTHESIS; MULTICOMPONENT SYNTHESIS; RAPID SYNTHESIS; EFFICIENT; RECEPTOR; ACCESS; P53; CONDENSATION; DERIVATIVES;

D O I：

10.1016/j.bioorg.2021.105464

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of imido-heterocycle compounds were designed, synthesized, characterized, and evaluated for the anticancer potential using breast (MCF-7 and MDA-MB-231), pancreatic (PANC-1), and colon (HCT-116 and HT-29) cancer cell lines and normal cells, while normal cells showed no toxicity. Among the screened compounds, 4h exhibited the best anticancer potential with IC50 values ranging from 1 to 5.5 mu M. Compound 4h caused G2/M phase arrest and apoptosis in all the cell lines except MDA-MB-231 mammosphere formation was inhibited. In vitro enzyme assay showed selective topoisomerase Ha inhibition by compound 4h, leading to DNA damage as observed by fluorescent staining. Cell signalling studies showed decreased expression of cell cycle promoting related proteins while apoptotic proteins were upregulated. Interestingly MDA-MB-231 cells showed only cytostatic effects upon treatment with compound 4h due to defective p53 status. Toxicity study using over-expression of dominant-negative mutant p53 in MCF-7 cells (which have wild type functional p53) showed that anticancer potential of compound 4h is positively correlated with p53 expression.

引用

页数：11

共 74 条

[1] An efficient synthesis of ferrocenyl imidazo[1,2-a]pyridines [J].

Akbarzadeh, Roya ;

Shakibaei, Ghazaleh Imani ;

Bazgir, Ayoob .

MONATSHEFTE FUR CHEMIE, 2010, 141 (10) :1077-1081

[2] Solvent-free Multicomponent Synthesis of Biologically-active Fused-imidazo Heterocycles Catalyzed by Reusable Yb(OTf)3 Under Microwave Irradiation [J].

Ansari, Arshad J. ;

Sharma, Shivani ;

Pathare, Ramdas S. ;

Gopal, Kandasamy ;

Sawant, Devesh M. ;

Pardasani, R. T. .

CHEMISTRYSELECT, 2016, 1 (05) :1016-1021

[3] Efficient Metal-Free Synthesis of Various Pyrido[2′,1′:2,3]imidazo- [4,5-b]quinolines [J].

Arnould, Mathieu ;

Hiebel, Marie-Aude ;

Massip, Stephane ;

Leger, Jean Michel ;

Jarry, Christian ;

Berteina-Raboin, Sabine ;

Guillaumet, Gerald .

CHEMISTRY-A EUROPEAN JOURNAL, 2013, 19 (37) :12249-12253

[4] Knoevenagel/Tandem Knoevenagel and Michael Adducts of Cyclohexane-1,3-dione and Aryl Aldehydes: Synthesis, DFT Studies, Xanthine Oxidase Inhibitory Potential, and Molecular Modeling [J].

Aror, Sahil ;

Joshi, Gaurav ;

Kalra, Sourav ;

Wani, Aabid Abdullah ;

Bharatam, Prasad, V ;

Kumar, Pradeep ;

Kumar, Raj .

ACS OMEGA, 2019, 4 (03) :4604-4614

[5] Cdk2 strengthens the intra-S checkpoint and counteracts cell cycle exit induced by DNA damage [J].

Bacevic, Katarina ;

Lossaint, Gerald ;

Achour, Thiziri Nait ;

Georget, Virginie ;

Fisher, Daniel ;

Dulic, Vjekoslav .

SCIENTIFIC REPORTS, 2017, 7

[6] Chemotherapy and signaling How can targeted therapies supercharge cytotoxic agents? [J].

Bagnyukova, Tetyana ;

Serebriiskii, Ilya G. ;

Zhou, Yan ;

Hopper-Borge, Elizabeth A. ;

Golemis, Erica A. ;

Astsaturov, Igor .

CANCER BIOLOGY & THERAPY, 2010, 10 (09) :843-857

[7] N-Fused Imidazoles As Novel Anticancer Agents That Inhibit Catalytic Activity of Topoisomerase IIα and Induce Apoptosis in G1/S Phase [J].

Baviskar, Ashish T. ;

Madaan, Chetna ;

Preet, Ranjan ;

Mohapatra, Purusottam ;

Jain, Vaibhav ;

Agarwal, Amit ;

Guchhait, Sankar K. ;

Kundu, Chanakya N. ;

Banerjee, Uttam C. ;

Bharatam, Prasad V. .

JOURNAL OF MEDICINAL CHEMISTRY, 2011, 54 (14) :5013-5030

[8]

Bedard PL, 2020, LANCET, V395, P1078, DOI 10.1016/S0140-6736(20)30164-1

[9] US FDA Approved Drugs from 2015-June 2020: A Perspective [J].

Bhutani, Priyadeep ;

Joshi, Gaurav ;

Raja, Nivethitha ;

Bachhav, Namrata ;

Rajanna, Prabhakar K. ;

Bhutani, Hemant ;

Paul, Atish T. ;

Kumar, Raj .

JOURNAL OF MEDICINAL CHEMISTRY, 2021, 64 (05) :2339-2381

[10] A novel dealkylation affording 3-aminoimidazo[1,2-a]pyridines:: access to new substitution patterns by solid-phase synthesis [J].

Blackburn, C ;

Guan, B .

TETRAHEDRON LETTERS, 2000, 41 (10) :1495-1500

← 1 2 3 4 5 6 7 8 →