Kumblekar Vasavi, Kumarchandra Reshma, Ranganath Pai K Sreedhara, K ShamaPrasada, Manandhar Suman, Shastry Rajeshwari, Rai Sharada
Department of Biochemistry, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India.
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Acaedemy of Higher Education, Manipal, Karnataka, 576104, India.
F1000Res. 2024 Dec 9;13:385. doi: 10.12688/f1000research.146862.3. eCollection 2024.
Breast cancer has become the most prevalent disease and its incidence has almost doubled in the Indian population. This increased burden demands new targeted therapies with novel compounds either synthetically produced or derived from indigenous plants, which could be a promising approach for the development of drugs. L is a widely growing tropical herb that has been reported to have various ethnopharmacological properties. Although Euphorbia genus is reported to have anticancer properties, is not reported to have anticancer properties to date. Therefore, the aim of the present study was to screen the phytoconstituents and identify the active compounds present in the methanolic extract of (ME.ET) as ligands to inhibit human cancer cell lines with special reference to potential protein targets implicated in breast cancer using an approach.
ME.ET was subjected to GC-MS analysis to screen the phytoconstituents, and the identified compounds were docked with protein targets such as extracellular signal-regulated kinases (ERK1), a serine/threonine kinase-1(AKT1), human epidermal growth factor 2 (HER2), estrogen receptor (ER), maternal embryonic leucine zipper kinase (MELK), polo-like kinase-1(PLK1), and protein tyrosine kinase (PTK6). Compounds with good docking scores were further subjected to dynamic studies to understand the protein ligand binding stability, ligand pathway calculation, and molecular mechanics energies combined with Poisson-Boltzmann (MM/PBSA) calculations using the Schrodinger suite.
GC-MS analysis revealed the presence of 245 phytoconstituents, 219 of which were unique. When subjected to docking, these phytocompounds, namely 3,6,9,12-tetraoxatetradecane-1,14-diyl dibenzoate (TTDB) and succinic acid, 2-(dimethylamino) ethyl 4-isopropylphenyl ester (SADPE), showed good docking scores. Molecular dynamics studies showed a high affinity and low binding energy for TTDB with HER2, ERK1, and SADPE with ER.
Hence, in this study, we identified two lead compounds in linn. Further and anticancer studies can be performed to confirm these results and to understand the molecular mechanism by which they exhibit anticancer activity against breast cancer.
乳腺癌已成为最普遍的疾病，其在印度人群中的发病率几乎翻了一番。这种日益增加的负担需要新的靶向治疗方法，使用合成生产的或源自本土植物的新型化合物，这可能是药物开发的一种有前景的方法。L是一种广泛种植的热带草本植物，据报道具有多种民族药理学特性。虽然大戟属植物据报道具有抗癌特性，但迄今为止尚未报道L具有抗癌特性。因此，本研究的目的是筛选植物成分，并鉴定L的甲醇提取物（ME.ET）中存在的活性化合物作为配体，以抑制人类癌细胞系，特别参考使用一种方法涉及乳腺癌的潜在蛋白质靶点。
对ME.ET进行气相色谱-质谱联用（GC-MS）分析以筛选植物成分，并将鉴定出的化合物与细胞外信号调节激酶（ERK1）、丝氨酸/苏氨酸激酶-1（AKT1）、人表皮生长因子2（HER2）、雌激素受体（ER）、母体胚胎亮氨酸拉链激酶（MELK）、波罗样激酶-1（PLK1）和蛋白酪氨酸激酶（PTK6）等蛋白质靶点进行对接。对接分数良好的化合物进一步进行动力学研究，以了解蛋白质-配体结合稳定性、配体途径计算以及使用薛定谔软件包结合泊松-玻尔兹曼（MM/PBSA）计算的分子力学能量。
GC-MS分析显示存在245种植物成分，其中219种是独特的。对接时，这些植物化合物，即3,6,9,12-四氧杂十四烷-1,14-二基二苯甲酸酯（TTDB）和琥珀酸2-（二甲基氨基）乙基4-异丙基苯基酯（SADPE），显示出良好的对接分数。分子动力学研究表明，TTDB与HER2、ERK1以及SADPE与ER具有高亲和力和低结合能。
因此，在本研究中，我们在Linn.中鉴定出两种先导化合物。可以进一步进行L的抗癌研究以证实这些结果，并了解它们对乳腺癌表现出抗癌活性的分子机制。
