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 the 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 azlactone synthesis. Twenty-one compounds were selected and screened at the 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 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 a potent anti-cancer agent as electron-rich moiety on phenyl at position 2 of triazine nucleus, having a great impact on anticancer activity.

Keywords: Cancer, anticancer screening, hydrazide, triazine, erlenmeyer plochl azalactone.