In Silico Discovery and ADMET Pharmacokinetic of Novel Pyrimidinic Selenoureas as Selective Breast Carcinoma Cells (MCF-7) Inhibitors

Abstract

Pyrimidine is one of aromatic heterocyclic class of organic compounds that’s similar to pyridine. It’s found in the nucleic acids DNA and RNA. Novel pyrimidinic selenoureas were reported to have a remarkable inhibitory activity against breast carcinoma cells (MCF-7). With the help of computer-aided drug design techniques one of these of compounds was further optimized to design three other derivatives with more potency than the previous and also more potent than many anti-breast cancer drugs. The main aim of this study was to design more potent pyrimidinic selenoureas derivatives and compare them with the standard anti-breast cancer drugs. An optimization method of structure-based drug design was employed. Two compounds of novel pyrimidinic selenoureas were reported in which the first compound was selected and docked with the ERBB2 receptor tyrosine kinase (PDB ID: 2A91), it was then modified to design three (3) derivatives. The receptors were later docked with seven (7) different anti-breast cancer drugs approved by American Cancer Society (such as, Capecitabine, Cisplatin, Curcumin, Paclitaxel, Ixabepilone, Doxorubicin and Vinorelbine) to record their potency and later compared with the designed compounds. An ADMET pharmacokinetic study was carried out on the designed compounds to investigate their drug-likeness. In the result, all the designed compounds were found to be more potent than the template, in which compound a1 and a2 (with moldock score of -148.456 and -153.725) were found to be more potent than Capecitabine, Cisplatin, Curcumin, Doxorubicin and Vinorelbine (moldock score; -134.953, -43.889, -148.290, -106.187 and -134.986), but less active than Paclitaxel and Ixabepilone (with moldock scores of -154.135 and -157.093), with compound a3 (moldock score; -161.583) recorded the highest potency which is more potent than all the listed drugs, and also the designed compounds were found to have good pharmacokinetic profiles. Conclusively, three other derivatives of novel pyrimidinic selenoureas were designed and found to be more potent than the template and many anti-breast cancer drugs. The compounds should be further synthesized for their excellent activities and good pharmacokinetic parameters.