Parallel synthesis of condensed pyrimidine-thiones and their antitumor activities

Herein, we studied the formation of thiones via C=O group conversion into C=S functional group-based tricyclic pyrimidinone systems using Lawesson’s reagent and phosphorus pentasulfide as thionation agents. Naturally occurring alkaloids deoxyvasicinone mackinazolinone were selected templates for modification furo[2,3-d]pyrimidinone pyrrolo[2,3-d]pyrimidinone scaffold. Research work was performed under combinatorial parallel synthesis pyrimidine-based small molecules, along with a one-pot reaction strategy. All synthesized 54 novel pyrimidine-thiones elucidated by 1H-NMR, 13C-NMR, HRMS analysis. In addition, both series evaluated their antitumor activity against three types human cancer cell: cervical HeLa, breast MCF-7, colon HT-29 lines. Compound azepine fragment 13aa (1-methyl-2-(4-(trifluoromethyl)phenyl)-1,6,7,8,9,10-hexahydro-4H-pyrrolo[2’,3’:4,5]pyrimido[1,2-a]azepine-4-thione) most active derivative (IC50 = 2.09 ± 0.22 µM) cell line.