Design and Synthesis of pyrimidine nucleus containing 4,6-disubstituted pyrimidine derivatives for the management of breast cancer

Abstract

It has been seen that Cancer is perhaps the most threatening diseases which cause major death in all over the globe. There are various types of cancer, such as lung cancer, breast, prostate, liver, skin, stomach and many more which may lead in the major death. Pyrimidine moiety is one of the important heterocyclic nucleuses having a wide scope of biological activity. A series of 4,6-disubstitutedpyrimidine-2-ones (4a-f) and 4,6-disubstitutedpyrimidine-2-thiones (5a-f) derivatives were synthesized using benzthiol, fluorobenzaldeyde and substituted acetophenones. Above derivatives utilized to discover dynamic derivatives and two arrangement of such dynamic compounds for example 4,6-disubstitutedpyrimidine-2-thiones and 4,6-disubstitutedpyrimidine-2-ones. The entire novel derivatives were analyzed and characterized by TLC, melting point analysis and spectral data studied by using FTIR, ¹H NMR, ¹³C NMR and Mass spectral data. The entire synthesized derivatives were screened against human breast tumor cell line (MCF7) for their in vitro anticancer activity by MTT assay method. The greater part of the prepared compounds displayed breast anti-cancer activity contrasted with Doxorubicin as a kind of reference medication. Compounds 4c, 4d 4f, 5b, 5c and 5f were showing significant cytotoxic potential properties with the IC₅₀ concentration at 13.09μg/ml, 8.53 μg/ml, 11.32 μg/ml, 10.85μg/ml, 9.74 μg/ml and 14.87 μg/ml respectively against breast cancer cell line compared to the standard drug Doxorubicin which was showing the IC₅₀ value at 7.51 μg/ml used for the study. Among all the synthesized compounds, 4d and 5c were found as most potent anticancer agent due to its low IC₅₀ value on MCF7 cells.