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 this compounds were further optimized to design three other derivatives with more potency than the previous and also more potent than many 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 was 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 1 and 2 (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), with compound 3 (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 parameters. Conclusively, three other derivatives of novel pyrimidinic selenoureas were designed and found to be more potent than the template and some selected anticancer drug.

Keywords: In silico Discovery, Novel pyrimidinic selenoureas, MCF-7 inhibitors, ADMET Pharmacokinetic.

Abbreviations: ADMET – Absorption, Distribution, Metabolism, Excretion and Toxicity, MCF-7 - breast carcinoma cells, PDB – Protein data bank.