Drug Res (Stuttg) 2019; 69(07): 406-414
DOI: 10.1055/a-0810-7033
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Synthesis of Novel Diaziridinyl Quinone Isoxazole Hybrids and Evaluation of Their Anti-Cancer Activity as Potential Tubulin-Targeting Agents

P. Ravi Kumar
1   Department of Medicinal Chemistry, GVK Biosciences Pvt. Ltd., Telangana, India
2   Centre for Chemical Sciences & Technology, Institute of Science and Technology, JNT University, Telangana, India
,
Satyanarayana Yennam
1   Department of Medicinal Chemistry, GVK Biosciences Pvt. Ltd., Telangana, India
,
K. Raghavulu
1   Department of Medicinal Chemistry, GVK Biosciences Pvt. Ltd., Telangana, India
,
Loka Reddy Velatooru
3   Biochemistry Department, School of life Sciences, University of Hyderabad, Telangana, India
,
Siva Reddy Kotla
3   Biochemistry Department, School of life Sciences, University of Hyderabad, Telangana, India
,
Vasudevarao Penugurti
3   Biochemistry Department, School of life Sciences, University of Hyderabad, Telangana, India
,
Prasanta K Hota
4   Department of Chemistry, School of Sciences, HNBG University, Uttarakhand, India
,
Manoranjan Behera
1   Department of Medicinal Chemistry, GVK Biosciences Pvt. Ltd., Telangana, India
,
A. Jaya Shree
2   Centre for Chemical Sciences & Technology, Institute of Science and Technology, JNT University, Telangana, India
› Author Affiliations
Further Information

Publication History

received 04 September 2018

accepted 29 November 2018

Publication Date:
17 January 2019 (online)

Abstract

Two series of diaziridinyl quinone isoxazole derivatives were prepared and evaluated for their cytotoxic activity against MCF7, HeLa, BT549, A549 and HEK293 cell lines and interaction with tubulin. Compounds (6a–m ) showed promising activity against all the 5 human cancer cell lines. Compounds 6a, 6e and 6 m were potent [IC50 ranging between 2.21 µg to 2.87 µg] on ER-positive MCF7 cell line similar to the commercially available drug molecule Doxorubicin. The results from docking models are in consistent with the experimental values which demonstrated the favourable binding modes of compounds 6a–m to the interface of α- and β-tubulin dimer.

Supplementary Material