Synthesis and biological evaluation of pyrazole linked benzothiazole-β-naphthol derivatives as topoisomerase I inhibitors with DNA binding ability

被引：51

作者：

Nagaraju, Burri ^{[1
,2
]}

Kovvuri, Jeshma ^{[1
,2
]}

Kumar, C. Ganesh ^{[1
,2
]}

Routhu, Sunitha Rani ^{[1
]}

Shareef, Md. Adil ^{[1
,2
]}

Kadagathur, Manasa ^{[1
]}

Adiyala, Praveen Reddy ^{[1
]}

Alavala, Sateesh ^{[1
]}

Nagesh, Narayana ^{[3
]}

Kamal, Ahmed ^{[1
,2
,4
]}

机构：

[1] CSIR Indian Inst Chem Technol, Med Chem & Biotechnol Div, Hyderabad 500007, Telangana, India

[2] Acad Sci & Innovat Res AcSIR, New Delhi 110025, India

[3] CSIR Ctr Cellular & Mol Biol, Hyderabad 500007, Telangana, India

[4] Jamia Hamdard, SPER, New Delhi 110062, India

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2019年 / 27卷 / 05期

关键词：

Pyrazole; Betanaphthol; Benzothiazole; Anticancer; DNA binding; Topoisomerase; POTENT; ANTITUMOR; LIGANDS; ANTICONVULSANT; CANCER; IDENTIFICATION; FLUORESCENCE; ANTAGONISTS; MECHANISMS; COMPLEXES;

D O I：

10.1016/j.bmc.2019.01.011

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 new pyrazole linked benzothiazole-beta-naphthol derivatives were designed and synthesized using a simple, efficient and ecofriendly route under catalyst-free conditions in good to excellent yields. These derivatives were evaluated for their cytotoxicity on selected human cancer cell lines. Among those, the derivatives 4j, 4k and 4l exhibited considerable cytotoxicity with IC50 values ranging between 4.63 and 5.54 mu M against human cervical cancer cells (HeLa). Structure activity relationship was elucidated by varying different substituents on benzothiazoles and pyrazoles. Further, flow cytometric analysis revealed that these derivatives induced cell cycle arrest in G2/M phase and spectroscopic studies such as UV-visible, fluorescence and circular dichroism studies showed that these derivatives exhibited good DNA binding affinity. Additionally, these derivatives can effectively inhibit the topoisomerase I activity. Viscosity studies and molecular docking studies demonstrated that the derivatives bind with the minor groove of the DNA.

引用

页码：708 / 720

页数：13

共 64 条

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