Parallel synthesis of condensed pyrimidine-thiones and their antitumor activities

Herein, we studied the formation of thiones via C=O group conversion into the C=S functional group-based tricyclic pyrimidinone systems using Lawesson’s reagent and phosphorus pentasulfide as thionation agents. Naturally occurring alkaloids deoxyvasicinone and mackinazolinone were selected as templates for the modification of furo[2,3- d ]pyrimidinone and pyrrolo[2,3- d ]pyrimidinone scaffold. Research work was performed under the combinatorial and parallel synthesis of pyrimidine-based small molecules, along with a one-pot reaction strategy. All synthesized 54 novel pyrimidine-thiones were elucidated by 1 H-NMR, 13 C-NMR, and HRMS analysis. In addition, both series of thiones were evaluated for their antitumor activity against three types of the human cancer cell: cervical HeLa, breast MCF-7, and colon HT-29 lines. Compound with azepine fragment 13aa (1-methyl-2-(4-(trifluoromethyl)phenyl)-1,6,7,8,9,10-hexahydro-4 H -pyrrolo[2’,3’:4,5]pyrimido[1,2- a ]azepine-4-thione) was most active derivative (IC 50 = 2.09 ± 0.22 µM) against the HT-29 cell line. Graphical abstract