Abstract
This investigation describes the design of a series of cycloheptathieno[2,3-d]pyrimidines along with their synthetic strategy. The target compounds were screened for their PARP-1 inhibitory activity. The modeling study declared that most of the docked compounds showed the same interactions as 3-aminobenzamide, where Gly 894, His 862, Tyr 896, Arg 878, and Ser 864 were the main residues involved in hydrogen bond formation. Compounds eliciting the top ranked docking results were screened for their PARP-1 inhibitory activity giving promising results, and three representative compounds were tested for their cytotoxic activity using Doxorubicin as a reference standard. The target compounds 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 including cyclohepta[b]thiophene and pentahydrocycloheptathieno[2,3-d]pyrimidine cores were designed, prepared, and tested for their PARP-1 inhibitory activity. Compounds 16 (R: ?NHC(S)NH2) and 11 (R: ?CS) were the most potent ones.