6533b871fe1ef96bd12d241e

RESEARCH PRODUCT

Synthesis, biological evaluation, and: In silico studies of novel chalcone: In pyrazoline-based 1,3,5-triazines as potential anticancer agents

Antonino LauriaBraulio InsuastyHenry InsuastyLeydi M. MorenoRodrigo AboniaJairo QuirogaAnnamaria Martorana

subject

ChalconeGeneral Chemical EngineeringCyanuric chloridePyrazolineTriazine derivatives01 natural sciencesClaisen Schmidt condensation03 medical and health scienceschemistry.chemical_compoundNucleophilic substitutionNucleophilic substitution030304 developmental biologyTriazinechemistry.chemical_classification0303 health sciences010405 organic chemistryLigandBiological evaluationGeneral ChemistryCondensation reactionCombinatorial chemistryCyclocondensation reaction0104 chemical sciencesEnzymechemistryAnticancer activitieThymidylate synthasePotential anticancer agent

description

A novel series of triazin-chalcones (7,8)a-g and triazin-N-(3,5-dichlorophenyl)pyrazolines (9,10)a-g were synthesized and evaluated for their anticancer activity against nine different cancer strains. Triazine ketones 5 and 6 were synthesized from the cyanuric chloride 1 by using stepwise nucleophilic substitution of the chlorine atom. These ketones were subsequently subjected to a Claisen-Schmidt condensation reaction with aromatic aldehydes affording chalcones (7,8)a-g. Then, N-(3,5-dichlorophenyl)pyrazolines (9,10)a-g were obtained by cyclocondensation reactions of the respective chalcones (7,8)a-g with 3,5-dichlorophenylhydrazine. Among all the evaluated compounds, chalcones 7d,g and 8g exhibited more potent in vitro anticancer activity, with outstanding GI50 values ranging from 0.422 to 14.9 μM and LC50 values ranging from 5.08 μM to >100 μM. In silico studies, for both ligand- and structure-based, were executed to explore the inhibitory nature of chalcones and triazine derivatives. The results suggested that the evaluated compounds could act as modulators of the human thymidylate synthase enzyme. This journal is

yearjournalcountryeditionlanguage
2020-01-01
10.1039/d0ra06799ghttp://hdl.handle.net/10447/493124