Maeruines A−E, elusive indole alkaloids from stems of Maerua siamensis and their inhibitory effects on cyclooxygenases and HT-29 colorectal cancer cell proliferation

• Published in: Phytochemistry (Oxford) Vol. 229; p. 114291
• Main Authors: Nukulkit, Sasiwimon, Nalinratana, Nonthaneth, Aree, Thammarat, Suriya, Utid, Suttisri, Rutt, Nuengchamnong, Nitra, Chang, Hsun-Shuo, Chansriniyom, Chaisak
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-01-2025
• Subjects: Capparaceae; Cyclooxygenases; HT-29 cell proliferation; Indole alkaloids; Maerua siamensis; Cyclooxygenases; Maerua siamensis; Capparaceae; Indole alkaloids; HT-29 cell proliferation
• ISSN: 0031-9422; 1873-3700; 1873-3700
• DOI: 10.1016/j.phytochem.2024.114291

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.
Maeruine D (4) displayed selective COX-2 inhibitory activity in vitro via hydrophobic interactions and significantly inhibited HT-29 colorectal cancer cell proliferation, induced by IL-1β. [Display omitted]
•Five alkaloids with imino-2H-thieno[2,3-b]indol-3(8H)-one skeleton were discovered.•Maeruine D displayed selective cyclooxygenase-2 inhibitory activity in vitro.•Maeruine D exhibited cytotoxicity against HT29 colorectal cancer cells.