Maeruines A-e，难以捉摸的吲哚生物碱来自Maerua Siamensis的茎及其对环氧酶和HT-29结直肠癌细胞增殖的抑制作用
Maeruines A-E, elusive indole alkaloids from stems of Maerua siamensis and their inhibitory effects on cyclooxygenases and HT-29 colorectal cancer cell proliferation
影响因子:3.40000
分区:生物学2区 / 生化与分子生物学2区 植物科学2区
发表日期:2025 Jan
作者:
Sasiwimon Nukulkit, Nonthaneth Nalinratana, Thammarat Aree, Utid Suriya, Rutt Suttisri, Nitra Nuengchamnong, Hsun-Shuo Chang, Chaisak Chansriniyom
摘要
从Maerua Siamensis的茎上获得了五个以前未描述的吲哚生物碱，即Maeruines A-E（1-5），带有Imino-2H-Thieno [2,3-B]吲哚-3（8H） - 一个骨骼。使用光谱技术[NMR，MS，IR和UV]和单晶X射线衍射阐明了它们的化学结构。 Maeruine D（4）在体外表现出选择性环氧合酶-2（COX-2）抑制活性，IC50为29.72±6.36μm。分子动力学模拟表明，Maeruine D可以与人Cox-2形成稳定的复合物，主要由疏水相互作用驱动。此外，五个氨基酸残基在内，包括Val349，Leu352，Leu384，Val523和Ala527被确定为热点，这可能会导致高结合亲和力和选择性。此外，它针对HT-29结直肠癌细胞表现出细胞毒性，IC50为29.32±4.76μm，在0.1-10μM下，以DOSE依赖性的方式，在0.1-10μM下显着抑制了它们的增殖，该促炎细胞因子金属蛋白金属蛋白金属蛋白金属蛋白金属蛋白毒素1β（IL-1β）诱导。
Abstract
Five previously undescribed indole alkaloids, maeruines A-E (1-5), bearing imino-2H-thieno[2,3-b]indol-3(8H)-one skeleton, were obtained from the stems of Maerua siamensis. Their chemical structures were elucidated using spectroscopic techniques [NMR, MS, IR, and UV], and single-crystal X-ray diffraction. Maeruine D (4) displayed selective cyclooxygenase-2 (COX-2) inhibitory activity in vitro with an IC50 of 29.72 ± 6.36 μM. Molecular dynamics simulations revealed that maeruine D could form a stable complex with human COX-2, predominantly driven by hydrophobic interactions. In addition, five amino-acid residues including Val349, Leu352, Leu384, Val523, and Ala527 were identified as hot-spot ones, which may lead to high binding affinity and selectivity. Furthermore, it exhibited cytotoxicity against HT-29 colorectal cancer cells with an IC50 of 29.32 ± 4.76 μM, and, at 0.1-10 μM, significantly inhibited their proliferation, induced by the proinflammatory cytokine interleukin-1β (IL-1β), in a dose-dependent manner.