Synthesis of new coumarin tethered isoxazolines as potential anticancer agents

Gejjalagere S Lingaraju; Kyathegowdanadoddi S Balaji; Shankar Jayarama; Seegehalli M Anil; Kuppalli R Kiran; Maralinganadoddi P Sadashiva

doi:10.1016/j.bmcl.2018.10.046

Synthesis of new coumarin tethered isoxazolines as potential anticancer agents

Bioorg Med Chem Lett. 2018 Dec 15;28(23-24):3606-3612. doi: 10.1016/j.bmcl.2018.10.046. Epub 2018 Oct 29.

Authors

Gejjalagere S Lingaraju¹, Kyathegowdanadoddi S Balaji², Shankar Jayarama², Seegehalli M Anil¹, Kuppalli R Kiran¹, Maralinganadoddi P Sadashiva³

Affiliations

¹ Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570 006, India.
² P.G. Department of Biotechnology, Teresian College, Mysore 570 011, India.
³ Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570 006, India. Electronic address: mpsadashiva@gmail.com.

PMID: 30396758
DOI: 10.1016/j.bmcl.2018.10.046

Abstract

A series of new coumarin tethered isoxazolines (7a-l) were synthesized and evaluated for their cytotoxic potency against human melanoma cancer cell line (UACC 903) as well as fibroblast normal cell line (FF2441). Preliminary results revealed that some of these coumarin tethered isoxazolines 7b, 7c, 7f and 7j exhibited significant antiproliferative effect against human melanoma cancer (UACC 903) with IC₅₀ values of 8.8, 10.5, 9.2 and 4.5 μM respectively. However, compound 7c was non-toxic to normal human cells at the tested concentration. Further, we have chosen compound 7c to check its efficacy in Ehrlich Ascites Carcinoma animal model in-vivo for its antitumor and antiangiogenic properties. Our lead compound significantly reduced the cell viability, body weight, ascites volume and downregulated the formation of neovasculature such as regression of tumor volume. The present study indicates the scope of developing into potent anticancer drug in near future.

Keywords: 1,3-Dipolar cycloaddition; Angiogenesis; Anticancer; Antiproliferative; Coumarin; Isoxazoline.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Angiogenesis Inhibitors / chemical synthesis
Angiogenesis Inhibitors / pharmacology
Angiogenesis Inhibitors / therapeutic use
Animals
Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use
Carcinoma, Ehrlich Tumor / drug therapy
Carcinoma, Ehrlich Tumor / mortality
Carcinoma, Ehrlich Tumor / pathology
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
Coumarins / chemistry*
Coumarins / pharmacology
Coumarins / therapeutic use
Disease Models, Animal
Humans
Isoxazoles / chemistry*
Microvessels / drug effects
Structure-Activity Relationship
Survival Rate

Substances

Angiogenesis Inhibitors
Antineoplastic Agents
Coumarins
Isoxazoles
coumarin