Department of Environmental Sciences, COMSATS University Islamabad, Abbottabad Campus 22060, Pakistan.
Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus 22060, Pakistan.
Biomed Res Int. 2022 May 14;2022:2941962. doi: 10.1155/2022/2941962. eCollection 2022.
Inorganic pollutant, specifically heavy metals' contamination, is a significant matter of concern and is one of the key contributors in various health disorders including cancer. However, the interaction of heavy metals (HMs) with lung cancer has rarely been explored yet. Therefore, the present study was intended with the aim to identify the interactions of HMs with the target protein "epidermal growth factor receptor (EGFR)" of lung cancer and explore potential drug candidates, which could inhibit the active site of EGFR against HM exposure. The molecular operating environment (MOE) tool was used to study the interactions of HMs with EGFR protein. The drug-drug interaction (DDI) network approach was used to identify the potential drug candidates, which were further confirmed and compared with the commercial medicines/control group. Various compounds of twenty-three HMs were docked with EGFR protein. Out of which tinidazole, thallium bromodimethyl, and silver acetate (Sn, Ti, and Ag compounds) showed strong interactions with EGFR based on lowest-scoring values (-20.42, -7.86, and -7.74 kcal/mol, respectively). Among 1280 collected drug candidates, three synthetic compounds viz., ZINC00602803, ZINC00602685, and ZINC06718468 and three natural compounds (berberine chloride, transresveratrol, and ellagic acid) depicted strong binding capacity with EGFR. Specifically, the scoring value of ZINC00602803 (-30.99 kcal/mol) was even lowest than standard lung cancer drugs (afatinib, erlotinib, and gefitinib). Our findings revealed that both natural and synthetic compounds having strong associations with EGFR protein could be potential candidates to inhibit the interaction between HMs and lung cancer protein and can also be used as an alternative for the prevention and treatment of lung cancer. However, and studies should be conducted to validate the aforementioned natural and synthetic compounds.
无机污染物，特别是重金属污染，是一个值得关注的重要问题，也是导致包括癌症在内的各种健康障碍的关键因素之一。然而，重金属（HM）与肺癌之间的相互作用尚未得到充分探讨。因此，本研究旨在确定 HM 与肺癌靶蛋白“表皮生长因子受体（EGFR）”的相互作用，并探索潜在的药物候选物，以抑制 EGFR 的活性位点对 HM 暴露的反应。使用分子操作环境（MOE）工具研究 HM 与 EGFR 蛋白的相互作用。采用药物-药物相互作用（DDI）网络方法来识别潜在的药物候选物，并对其进行进一步验证和与商业药物/对照组进行比较。对 23 种 HM 的各种化合物进行了 EGFR 蛋白的对接。其中，替硝唑、溴二甲汞和醋酸银（Sn、Ti 和 Ag 化合物）基于最低评分值（分别为-20.42、-7.86 和-7.74 kcal/mol）与 EGFR 表现出强烈的相互作用。在收集的 1280 种药物候选物中，三种合成化合物 ZINC00602803、ZINC00602685 和 ZINC06718468 以及三种天然化合物（盐酸小檗碱、反式白藜芦醇和鞣花酸）与 EGFR 表现出强烈的结合能力。具体而言，ZINC00602803 的评分值（-30.99 kcal/mol）甚至低于标准肺癌药物（阿法替尼、厄洛替尼和吉非替尼）。我们的研究结果表明，与 EGFR 蛋白具有强烈关联的天然和合成化合物都可能成为抑制 HM 与肺癌蛋白相互作用的潜在候选物，并可作为预防和治疗肺癌的替代方法。然而，需要进一步进行和研究来验证上述天然和合成化合物。
