Synthesis of Novel 1,2-Dihydro-1,2,4-Triazin-6(5H)-one Derivatives as Anticancer Agents

Abstract

Introduction: Cancer is still an untreatable disease and the second leading cause of death globally. The heterocyclic compounds have always played a major role in anticancer drug discovery program. 1,2,4-Triazine-6-ones is a heterocyclic privileged structure with diversified activities. In the presented study 21 Novel 2,5-disubstituted-3-phenyl-1,2-dihydro-1,2,4-triazin-6 (5H)-one derivatives (13(a-k), 18(a-j) and 21(a1-a4, b)) have been synthesized and tested for their anticancer activity. Methods: The 2,5-disubstituted-3-phenyl-1,2-dihydro-1,2,4-triazin-6(5H)-one derivatives (13(a-k), 18(a-j) and 21(a1-a4, b) were synthesized by refluxing substituted-2-phenyloxazol-5(4H)-one and hydrazine derivatives. Substituted aldehydes were synthesized via Vilsmeier-Haack reaction, while substituted-2-phenyloxazol-5(4H)-one derivatives were synthesized by Erlenmeyer Plochl azalactone synthesis. Twenty-one compounds were selected and screened at National Cancer Institute (NCI), USA for anticancer activity at a single high dose (10-5M) in full NCI 60 cell panel assay. Results and Conclusion: The selected compounds (13a, 13b, 13c, 13f, 13h, 13i, 13j, 18h, 18i, 21a4) were found to be an active against different cancer cell lines. The compound, 5-((5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)methylene)-2-(4-nitrobenzoyl)-3-phenyl-1,2-dihydro-1,2,4-triazin-6(5H)-one (13a) was found to be potent anti-cancer agent as electron rich moiety on phenyl at position 2 of triazine nucleus has great impact on anticancer activity.