Centre for Natural Products & Traditional Knowledge, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad, 500007, India.
Applied Biology Department, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India.
Eur J Med Chem. 2020 Feb 15;188:111974. doi: 10.1016/j.ejmech.2019.111974. Epub 2019 Dec 18.
A series of 28 novel 1,2,3-triazole hybrids of myrrhanone B have been designed and synthesized by employing regioselective Cu catalyzed Huisgen 1,3-dipolar cycloaddition reaction in highly efficient manner. All the synthesized analogues were assessed for their antiproliferative potential against A549 (Lung), DU145 (Prostate), MDA-MB-231 (Breast), SiHa (Cervical), U87MG (Glioblastoma), PC-3 (Prostate), HT-29 (Colon), L132 (Normal lung) cell lines. Further, the synthesized hybrids have also been screened for anti-inflammatory activity (TNF-α and IL-1β) and α-glucosidase inhibitory activity. The biological results revealed that compound 11 (meta hydroxy phenyl 1,2,3-triazole) and compound 29 (deoxyuridine 1,2,3-triazole) found to be the most potent antiproliferative ones against PC-3 cell line. Compound 11 (IC: 6.57 ± 0.62 μM) showed six folds more potent than parent compound 1 (IC: 40.67 ± 2.2 μM) and displayed almost identical inhibitory activity with standard doxorubicin (IC: 5.05 ± 0.25 μM), whereas compound 29 (IC: 10.85 ± 0.90 μM) exhibited four folds more potent than parent myrrhanone B (1). In view of potent activity of compounds 11 and 29 they have been subjected to detailed flowcytometry analysis. Compound 29 treated cells significantly increased the SubG1 population of cells indicative of apoptosis compared to compound 11. Further, the results of anti-inflammatory studies indicated that compounds 3, 6, 9, 27, 28, 29 and 30 exhibited significant inhibitory activity against both TNF-α and IL-1β than the parent compound 1. Interestingly, compound 27 exhibited good activity towards inflammatory cytokines TNF-α (IC: 7.83 ± 0.95 μM). Interestingly, α-glucosidase inhibitory assay results revealed that compounds 14 (IC: 2.77 ± 0.59 μM) and 16 (IC: 4.12 ± 0.77 μM) as the most potent ones. In fact, compound 14 exhibited highest activity and found to be several times more potent than the parent compound 1 as well as standard acarbose (IC: 2124 ± 170 μM).
已经通过区域选择性 Cu 催化的 Huisgen 1,3-偶极环加成反应以高效方式设计和合成了一系列 28 种新型 1,2,3-三唑混合麦角酮 B。所有合成的类似物均针对 A549（肺）、DU145（前列腺）、MDA-MB-231（乳腺）、SiHa（宫颈）、U87MG（神经胶质瘤）、PC-3（前列腺）、HT-29（结肠）、L132（正常肺）细胞系进行了抗增殖潜力评估。此外，还对合成的杂种进行了抗炎活性（TNF-α和 IL-1β）和α-葡萄糖苷酶抑制活性筛选。生物结果表明，化合物 11（间羟基苯基 1,2,3-三唑）和化合物 29（脱氧尿苷 1,2,3-三唑）被发现对 PC-3 细胞系具有最强的抗增殖作用。化合物 11（IC：6.57±0.62μM）的效力比母体化合物 1（IC：40.67±2.2μM）高六倍，并且与标准阿霉素（IC：5.05±0.25μM）的抑制活性几乎相同，而化合物 29（IC：10.85±0.90μM）的效力比母体麦角酮 B（1）高四倍。鉴于化合物 11 和 29 的强大活性，对其进行了详细的流式细胞术分析。与化合物 11 相比，用化合物 29 处理的细胞明显增加了细胞的 SubG1 群体，表明细胞凋亡。此外，抗炎研究结果表明，化合物 3、6、9、27、28、29 和 30 对 TNF-α和 IL-1β的抑制活性均优于母体化合物 1。有趣的是，化合物 27 对炎症细胞因子 TNF-α（IC：7.83±0.95μM）表现出良好的活性。有趣的是，α-葡萄糖苷酶抑制测定结果表明，化合物 14（IC：2.77±0.59μM）和 16（IC：4.12±0.77μM）是最有效的化合物。事实上，化合物 14 的活性最高，与母体化合物 1 以及标准阿卡波糖（IC：2124±170μM）相比，其效力高出数倍。
