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

P. Ravi Kumar; Satyanarayana Yennam; K. Raghavulu; Loka Reddy Velatooru; Siva Reddy Kotla; Vasudevarao Penugurti; Prasanta K Hota; Manoranjan Behera; A. Jaya Shree

doi:10.1055/a-0810-7033

Drug Research, Inhaltsverzeichnis

Drug Res (Stuttg) 2019; 69(07): 406-414
DOI: 10.1055/a-0810-7033

Original Article

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

P. Ravi Kumar

¹Department of Medicinal Chemistry, GVK Biosciences Pvt. Ltd., Telangana, India

²Centre for Chemical Sciences & Technology, Institute of Science and Technology, JNT University, Telangana, India

,

Satyanarayana Yennam

¹Department of Medicinal Chemistry, GVK Biosciences Pvt. Ltd., Telangana, India

,

K. Raghavulu

¹Department of Medicinal Chemistry, GVK Biosciences Pvt. Ltd., Telangana, India

,

Loka Reddy Velatooru

³Biochemistry Department, School of life Sciences, University of Hyderabad, Telangana, India

,

Siva Reddy Kotla

³Biochemistry Department, School of life Sciences, University of Hyderabad, Telangana, India

,

Vasudevarao Penugurti

³Biochemistry Department, School of life Sciences, University of Hyderabad, Telangana, India

,

Prasanta K Hota

⁴Department of Chemistry, School of Sciences, HNBG University, Uttarakhand, India

,

Manoranjan Behera

¹Department of Medicinal Chemistry, GVK Biosciences Pvt. Ltd., Telangana, India

,

A. Jaya Shree

²Centre for Chemical Sciences & Technology, Institute of Science and Technology, JNT University, Telangana, India

› Institutsangaben

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.

Key words

isoxazole - quinone - aziridine - diaziridinyl quinone isoxazole - cytotoxicity - molecular docking

Volltext

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