Background: The breast cancer takes the first place among women cancer diagnosed worldwide.

Objective: Based on the preferential multi-targeted approach to cancer therapy, we, in this study, aimed to design in silico drug candidates possessing multi-targeted bioactivity to cope with multidrug resistance using the known drug structures, molecular modeling, and ADME parameters.

Materials and Methods: We first evaluated the bioactivity score of the approved breast cancer drugs across the top-three drug targets GPCR, kinase, and nuclear receptors and calculated their physicochemical properties to see their drug-likeness profiles. Among 29 approved drugs, Aromasin and Capecitabine showed the broadest bioactivity across the targets listed. By using molecular modeling and bioisosteric modifications, and applying two filtering approaches, we investigated thirty-one analogues of Aromasin and Capecitabine.

Results: Software prediction resulted in that the compounds A14, C4, and C13 replaced with B(OH)₂ and/or Si(CH₃)₃ showed a broader spectrum of biological activity with a multi-targeted manner than even the approved analogs.

Conclusion: The interesting point of these new design molecules is to have either silicon and/or boron incorporation. The increased bioactivity effect of Silicon and Boron incorporation is also seen in the recently approved drug list of FDA and in clinical trials ongoing. Our new design boron and silicon-based molecules appeared to be promising candidates for breast cancer treatment to be tested in vitro, in vivo, and in the clinic for further pharmacological investigations.

背景：乳腺癌在全球确诊的女性癌症中位居首位。

目的：基于优先的多靶向癌症治疗方法，我们在本研究中旨在利用已知的药物结构、分子模型和 ADME 参数设计具有多靶向生物活性的计算机候选药物以应对多药耐药性。

材料和方法：我们首先评估了前三大药物靶点 GPCR、激酶和核受体的获批乳腺癌药物的生物活性评分，并计算了它们的理化特性以查看它们的药物相似性特征。在 29 种获批药物中，Aromasin 和卡培他滨在所列靶标中表现出最广泛的生物活性。通过使用分子建模和生物等排修饰，并应用两种过滤方法，我们研究了 Aromasin 和卡培他滨的 31 种类似物。

结果：软件预测结果表明，用 B(OH) ₂和/或 Si(CH ₃ ) ₃代替的化合物 A14、C4 和 C13显示出比已批准的类似物更广泛的多靶向方式的生物活性谱。

结论：这些新设计分子的有趣之处在于具有硅和/或硼的结合。在 FDA 最近批准的药物清单和正在进行的临床试验中也可以看到硅和硼掺入增加的生物活性效果。我们新设计的硼和硅基分子似乎是乳腺癌治疗的有希望的候选者，可在体外、体内和临床中进行进一步的药理学研究。