Drosophila Laboratory, Department of Biochemistry, University of Ibadan, Ibadan, Oyo State, Nigeria.
Drosophila Research and Training Centre, Ibadan, Oyo State, Nigeria.
Appl Biochem Biotechnol. 2023 Dec;195(12):7159-7175. doi: 10.1007/s12010-023-04473-2. Epub 2023 Mar 29.
The BRCA1 and BRCA2 are genes that encode a protein that ensures the integrity of DNA and prevents the unregulated cells from proliferating. Mutations in the sequence of these genes are associated with the birth of inherited breast cancers. The research for possible human breast cancer treatment remains a vital step in the drug development process. In this study, in silico investigations involving a computational method for the discovery of active phytochemicals from Carica papaya against the BRCA-1 gene were carried out. The in silico studies for these phytochemicals datasets as BRCA-1 breast cancer therapeutic agents showed promising results through pharmacokinetics and pharmacodynamics studies. The Carica papaya compounds were found to follow the rule of five and have good bioavailability. The ADMET and drug-likeness screening score of the identified ligands also recognized their potential as a promising drug candidate against BRCA-1 while the DFT also confirm better biological and chemical reactivity of Carica papaya compounds with excellent intra-molecular charge transfer between electron donor and electron acceptor site. The results of the molecular docking provided useful information on possible target-lead interactions, demonstrating that the newly developed leads showed a high affinity for BRCA-1 targets and might be investigated for further research.
BRCA1 和 BRCA2 是编码一种蛋白质的基因，该蛋白质可确保 DNA 的完整性并防止不受控制的细胞增殖。这些基因序列中的突变与遗传性乳腺癌的发生有关。寻找可能的人类乳腺癌治疗方法仍然是药物开发过程中的重要步骤。在这项研究中，对从 Carica papaya 中发现针对 BRCA-1 基因的活性植物化学物质的计算方法进行了计算机模拟研究。通过药代动力学和药效学研究，这些植物化学物质数据集作为 BRCA-1 乳腺癌治疗剂的计算机模拟研究显示出了有希望的结果。发现 Carica papaya 化合物符合五规则，并具有良好的生物利用度。所鉴定配体的 ADMET 和类药性筛选评分也确认了它们作为针对 BRCA-1 的有前途的候选药物的潜力，而 DFT 还证实了 Carica papaya 化合物具有更好的生物和化学反应性，在电子供体和电子受体位点之间具有出色的分子内电荷转移。分子对接的结果提供了有关可能的靶标 - 配体相互作用的有用信息，表明新开发的配体对 BRCA-1 靶标具有高亲和力，可能会进一步研究。
