TY - JOUR
T1 - Maeruines A−E, elusive indole alkaloids from stems of Maerua siamensis and their inhibitory effects on cyclooxygenases and HT-29 colorectal cancer cell proliferation
AU - Nukulkit, Sasiwimon
AU - Nalinratana, Nonthaneth
AU - Aree, Thammarat
AU - Suriya, Utid
AU - Suttisri, Rutt
AU - Nuengchamnong, Nitra
AU - Chang, Hsun Shuo
AU - Chansriniyom, Chaisak
N1 - Publisher Copyright:
© 2024 Elsevier Ltd
PY - 2025/1
Y1 - 2025/1
N2 - 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.
AB - 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.
KW - Capparaceae
KW - Cyclooxygenases
KW - HT-29 cell proliferation
KW - Indole alkaloids
KW - Maerua siamensis
UR - http://www.scopus.com/inward/record.url?scp=85204773669&partnerID=8YFLogxK
U2 - 10.1016/j.phytochem.2024.114291
DO - 10.1016/j.phytochem.2024.114291
M3 - Article
AN - SCOPUS:85204773669
SN - 0031-9422
VL - 229
JO - Phytochemistry
JF - Phytochemistry
M1 - 114291
ER -