A facile one-pot expeditious synthesis of triazolothiadiazines and anticancer activity

Abstract

A novel, one-pot, multicomponent synthesis of triazolothiadiazine derivatives have been achieved starting from 4-amino-4H-1,2,4-triazole-3,5-dithiol and variously substituted phenacyl bromides. The synthesis involves the simultaneous formation of two C–S and one C = N bond. The newly synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR, and mass spectral data. The advantages of this method are good yields, high purity, shorter reaction times and simple purification technique. The synthesized target compounds were screened for their in vitro anticancer activity at concentration 10⁻⁵ M against 60 cancer cell lines. Among all the compounds, 1-(4-Fluorophenyl)-2-((6-(4-fluorophenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl) thio)ethanone (4d), 1-(4-Bromophenyl)-2-((6-(4-bromophenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl)thio) ethanone (4f), and 2-((6-(4-Chlorophenyl)-7H-[1,2,4] triazolo[3,4-b][1,3,4]thiadiazin-3-yl)thio)-1-(4-fluorophenyl)ethanone (4l) exhibited significant activity in terms of growth percent against renal cancer OU-31 cell line with 47.42%, 46.76%, 48.14%. The compound 2-((6-(4-Chlorophenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl)thio)-1-(4-fluorophenyl) ethanone (4l) also exhibited significant activity on leukemia MOLT-4 cell line with 49.82%.

Graphical Abstract

Keywords:

• Traiazolothiadiazines
• phenacyl bromides
• multicomponent approach
• anticancer activity

Acknowledgments

Author VA grateful to the University Grants Commission (UGC) –New Delhi for providing research fellowship and also thankful to the Director, National Institute of Technology-Warangal, T.S., India for providing the research facilities. The authors also thankful to the National Cancer Institute (NCI), the USA for screening the compounds for their anticancer activity.