从链霉菌 MR28 中提取的黑色素对黑素瘤致 MITF 蛋白的计算机分子对接研究及其抗癌、氧化还原、光保护和药物结合特性
In Silico Molecular Docking Approach of Melanin Against Melanoma Causing MITF Proteins and Anticancer, Oxidation-Reduction, Photoprotection, and Drug-Binding Affinity Properties of Extracted Melanin from Streptomyces sp. strain MR28.
机构信息
P.G. Department of Studies in Botany, Karnatak University, Dharwad, Karnataka, 580003, India.
Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia.
出版信息
Appl Biochem Biotechnol. 2023 Jul;195(7):4368-4386. doi: 10.1007/s12010-023-04358-4. Epub 2023 Jan 24.
Melanin is a biopolymer reported for diverse biological actions to secure organisms over adverse environmental factors. In the last decade, melanin attributed considerable attention for its use in bioelectronics, photoprotection, environmental bioremediation, and drug discovery. Molecular docking study is the emerging trend in drug discovery for drug designing by targeting proteins. Considering the therapeutic nature of the melanin, we extracted melanin from Streptomyces sp. strain MR28, and it was tested for various biological activities, viz., DPPH free radical scavenging potency, sun protection factor (SPF), drug likeness by SwissADME, molecular docking of melanin on melanocyte-inducing transcription factor (MITF) proteins, cytotoxic activity on A375 malignant melanoma with induction of apoptosis study by flow cytometry, and adsorption study of melanin on doxorubicin and camptothecin drug for drug uptake by melanin. The melanin showed good scavenging potency of DPPH free radicals in a concentration-dependent manner. SPF of 38.64 ± 0.63, 55.53 ± 0.53, and 67.07 ± 0.82 were recorded at 0.06, 0.08, and 0.1 µg/mL, concentrations, respectively. SwissADME screening confirms the drug likeness of melanin. Docking of melanin with MITF proteins exhibited a maximum of - 9.2 kcal/mol binding affinity for 4ATK protein. Cytotoxicity of the melanin drug exhibited good inhibition of melanoma cells in dose-dependent way with significant IC of 65.61 µg/mL; apoptotic study reveals melanin showed 64.02% apoptosis for melanin and 33.8% apoptosis for standard drug (doxorubicin). The maximum adsorptions for selected drugs camptothecin and doxorubicin to melanin were recorded at 90 min. In conclusion, the extracted melanin showed significant results over many biological applications and it can be used in the pharmaceutical field to avoid chemical-based drugs.
黑色素是一种生物聚合物,据报道具有多种生物作用,可以保护生物体免受不利环境因素的影响。在过去的十年中,黑色素因其在生物电子学、光保护、环境生物修复和药物发现中的应用而受到极大关注。分子对接研究是药物设计中针对蛋白质的一种新兴趋势。考虑到黑色素的治疗性质,我们从链霉菌属 MR28 菌株中提取黑色素,并测试了它的各种生物活性,即 DPPH 自由基清除能力、防晒因子 (SPF)、瑞士 ADME 的药物相似性、黑色素对黑色素生成诱导转录因子 (MITF) 蛋白的分子对接、对 A375 恶性黑色素瘤的细胞毒性活性以及通过流式细胞术诱导细胞凋亡研究的黑色素诱导的细胞毒性活性,以及黑色素对阿霉素和喜树碱药物的吸附研究以增加黑色素的药物摄取。黑色素在浓度依赖性方式下显示出良好的 DPPH 自由基清除能力。在 0.06、0.08 和 0.1μg/mL 浓度下,记录到 SPF 分别为 38.64±0.63、55.53±0.53 和 67.07±0.82。瑞士 ADME 筛选证实黑色素具有药物相似性。黑色素与 MITF 蛋白的对接显示,在 4ATK 蛋白上的最大结合亲和力为-9.2 kcal/mol。黑色素药物的细胞毒性在剂量依赖性方式下对黑色素瘤细胞表现出良好的抑制作用,其 IC 为 65.61μg/mL;凋亡研究表明,黑色素对黑色素的凋亡率为 64.02%,对标准药物(阿霉素)的凋亡率为 33.8%。选定药物喜树碱和阿霉素对黑色素的最大吸附率在 90 分钟时达到。总之,提取的黑色素在许多生物应用中表现出显著的效果,可用于制药领域以避免使用基于化学的药物。