Six series based on barbituric acid 5a-e, 10a-d; thiobarbituric acid 6a-e, 11a-d and 1,3-dimethylbarbituric acid 7a-e, 12a-d were prepared and screened for their in vitro PARP1 inhibition. They revealed promising inhibition at nanomolar level especially compounds 5c, 7b, 7d and 7e (IC = 30.51, 41.60, 41.53 and 36.33 nM) with higher potency than olaparib (IC = 43.59 nM). Moreover, compounds 5b, 5d, 7a, 12a and 12c exhibited good comparable activity (IC = 65.93, 58.90, 66.57, 45.40 and 50.62 nM, respectively). Furthermore, the most active compounds 5c, 7b, 7d, 7e, 12a and 12c against PARP1 in vitro were evaluated in the BRCA1 mutated triple negative breast cancer cell line MDA-MB-436 where 5c and 12c showed higher potency compared to olaparib and result in cell cycle arrest at G2/M phase. 5c and 12c showed apoptotic effects in MDA-MB-436 and potentiated the cytotoxicity of temozolomide in A549 human lung epithelial cancer cell line. Compounds 5c and 12c represent interesting starting points towards PARP1 inhibitors.

n/a

The density matrix expansion method, together with three different effective nucleon-nucleon forces, is used to calculate the real part of the interaction potential between two 16O nuclei. The densities of the system are constructed using two different methods. In the first, a two-centre harmonic-oscillator potential is employed to construct the density and the kinetic energy density of the combined system and of the separated nuclei. In the second method, the density of the combined system is assumed to be the sum of the two separate densities and the kinetic energy densities are given approximately by the Thomas-Fermi approximation. The authors have found that the ion-ion potential derived using the second method shows a stronger energy dependence than that derived from the first. A comparison between the ion-ion potentials in the relevant tail region also showed that the second method includes, at zero energy, 30-60% of the exchange effects due to antisymmetrisation for the Negele force. At the same energy and for the Skyrme force the second method can be considered to be a very good approximation to the first.