Synthesis of New 4,5-Dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-amine–Derived Ureas and Their Anticancer Activity

Abstract

A new series of 1,2,4-triazolo[4,3-a]-quinoline derivatives were designed and synthesized to meet the structural requirements essential for anticancer activity. N-1-(5-Methylisoxazol-4-yl/4-fluoro-2,3-dihydro-1H-inden-1-yl/aryl)-N’-3-(4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-yl) urea derivatives were accomplished in good yields by the reaction of 4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-amine with 3-(3-chloro-5-fluoro-2-methoxyphenyl)-5-methyl-isoxazole-4-carboxylic acid, 4-fluoro-2,3-dihydro-1H-indene-1-carboxylic acid, and various simple aromatic carboxylic acids in the presence of diphenyl phosphoryl azide (DPPA). All the newly synthesized title compounds were characterized by elemental and spectral data. Furthermore, anticancer activity was screened for the title compounds (12a–j) in vitro against human neuroblastoma cell lines (SK N SH) and human colon carcinoma cell lines (COLO 205) by using the MTT cell viability method. A few of them (12a and 12b) possess significant cytotoxicity, and some other compounds 12d-f and 12j displayed moderate cytotoxicity against both cell lines.

GRAPHICAL ABSTRACT

Keywords:

• Anticancer activity
• 3-(3-chloro-5-fluoro-2-methoxyphenyl)-5-methyl-isoxazole-4-carboxylic acid
• 4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-amine
• diphenyl phosphoryl azide
• 4-fluoro-2,3-dihydro-1H-indene-1-carboxylic acid

ACKNOWLEDGMENTS

The authors acknowledge A. V. Ramana Reddy, analytical chemistry head, BARC, Mumbai, for his fruitful discussions of this project. Finally we profusely thank V. Ramakrisna, Department of Biotechnology and Bioinformatics, Yogi Vemana University, Kadapa, for the screening of anticancer activity.