Background: The concept of synthetic lethality is an emerging field in the treatment of cancer and can be applied for new drug development of cancer as already been represented by Poly (ADP-ribose) polymerase (PARPs) inhibitors.

Objective: In this study, we performed virtual screening of 329 flavonoids obtained from the Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target (NPACT) database to identify novel PARP inhibitors.

Materials and Methods: Virtual screening carried out using different in silico methods which include molecular docking studies, prediction of drug-likeness and in silico toxicity studies.

Results: Fifteen out of 329 flavonoids achieved better docking score as compared to rucaparib which is an FDA approved PARP inhibitor. These 15 hits were again rescored using accurate docking mode and drug-likeliness properties were evaluated. The accuracy of the docking method was checked using re-docking. Finally NPACT00183 and NPACT00280 were identified as potential PARP inhibitors with docking score of -139.237 and -129.36, respectively. These two flavonoids also showed no AMES toxicity and no carcinogenicity which was predicted using admetSAR.

Conclusion: Our finding suggests that NPACT00183 and NPACT00280 have promising potential to be further explored as PARP inhibitors.

背景：合成致死的概念是癌症治疗中的一个新兴领域，可用于癌症的新药开发，以聚（ADP-核糖）聚合酶（PARPs）抑制剂为代表。

目的：在这项研究中，我们对从天然存在的基于植物的抗癌化合物-活性-靶点 (NPACT) 数据库中获得的 329 种黄酮类化合物进行了虚拟筛选，以识别新型 PARP 抑制剂。

材料和方法：使用不同的计算机方法进行虚拟筛选，包括分子对接研究、药物相似性预测和计算机毒性研究。

结果：与 FDA 批准的 PARP 抑制剂 rucaparib 相比，329 种黄酮类化合物中有 15 种获得了更好的对接评分。使用准确的对接模式再次对这 15 次命中进行重新评分，并评估了药物相似性。使用重新对接检查对接方法的准确性。最后，NPACT00183 和 NPACT00280 被确定为潜在的 PARP 抑制剂，对接评分分别为 -139.237 和 -129.36。这两种黄酮类化合物也没有显示出 AMES 毒性和使用 admetSAR 预测的致癌性。

结论：我们的发现表明 NPACT00183 和 NPACT00280 具有作为 PARP 抑制剂进一步探索的潜力。